AJH
1991;
4:570-578
Bengt Κ Widgren, Hans Herlitz, Thomas Hedner, Goran Berglund, John Wikstrand, Olof Jonsson, and Ove K. Andersson
The natriuretic and intra-arterial blood pressure re sponse to an acute saline load (1000 mL 0.9% NaCl), was studied in normotensive young men with posi tive (n = 11) and negative (n = 21) family histories of hypertension. The age-matched (36 ± 5 years) control group with negative family histories of hy pertension was subdivided into two groups, one matched for body mass index (BMI) to the subjects with positive family histories of hypertension (n = 10), and another lean control group (n = 11). Baseline blood pressure was significantly higher in subjects with positive family histories of hyper tension and in controls matched for BMI as com pared with lean controls. Sodium excretion in creased in all three groups during the saline infusion, while subjects with positive family histo ries of hypertension disclosed a diminished na triuretic response as compared with the two control groups. Systolic blood pressure increased signifi cantly during the saline load in subjects with positive family histories of hypertension, while
A
reduced intrinsic ability of the kidney to ex crete sodium and water has been suggested to be an inherited pathogenetic factor in pri mary hypertension. Lever et al, on the other 1
2
From the Department of Medicine, Hypertension Unit (BRW, HH, GB, OKA), Department of Clinical Pharmacology (TH), the Wallen berg Laboratory for Cardiovascular Research (JW), and the Depart ment of Surgery (OJ), Sahlgrenska Hospital, University of Gothen burg, Göteborg, Sweden. Prof. G. Berglund is now with the Department of Medicine, Malmö General Hospital, University of Lund, Malmö, Sweden. Address correspondance and reprint requests to Bengt R. Widgren, Department of Medicine, Hypertension Unit, Sahlgrenska Hospital, S-413 45 Göteborg, Sweden.
© 1991 by the American Journal of Hypertension, Inc.
in subjects with negative family histories of hyper tension, no significant change in blood pressure was observed. Plasma renin activity, angiotensin II, serum aldosterone, plasma noradrenaline, blood volume, and ouabain-sensitive erythrocyte sodium efflux rate constant did not differ between the three groups at baseline. A significant negative correlation was found between baseline sodium ex cretion and sodium efflux rate constant in subjects with positive family histories of hypertension. We conclude that the subjects with positive fam ily histories of hypertension exhibit a blunted na triuretic and an exaggerated blood pressure re sponse to an acute saline load as compared with the two control groups with negative family histories of hypertension. This could be of neuronal and/or hormonal origin. Am J Hypertens 1991;4:570-578 KEY WORDS: Family history of hypertension, renal sodium excretion, pressor response, sympathetic ac tivity, sodium efflux rate constant.
hand, proposed that hypertensive patients are charac terized by an abnormal sodium handling which was not due to a primary renal disturbance but rather to a lesion as a consequence of the hypertension. However, in sev eral studies patients with primary hypertension have responded to intravenous saline infusion with a more pronounced natriuresis than that in normotensive sub jects. The pathophysiologic basis for this response is not clear but a high blood pressure and low renin seems to be a prerequisite. In contrast, in hypertensives with normal renin a blunted natriuresis to saline load was reported. Substantial evidence exists that subjects with positive 3
4
5
0895-7061/91/$3.50
Downloaded from http://ajh.oxfordjournals.org/ at The University of British Colombia Library on October 14, 2015
Blunted Renal Sodium Excretion During Acute Saline Loading in Normotensive Men With Positive Family Histories of Hypertension
AJH-JULY
1991-VOL
4, NO. 7, PART 1
RENAL SODIUM HANDLING AND FAMILY HISTORIES OF HYPERTENSION
6-9
10
11
12,13
14
15
16
17
18,19
20
21-24
25
10
26-28
29-31
32,33
34
followed for many years at our outpatient hypertension unit. These hypertensive fathers had both of their par ents treated for hypertension or had a history of stroke before the age of 65 years. The control group with nega tive family histories of hypertension were recruited from the same study cohort among the sons of normo tensive fathers without family histories of hypertension or stroke. Selection procedures and cardiovascular characteristics of the parents of the examined young men have been described in detail elsewhere. In the group with positive family histories of hyper tension four subjects refused catheterization. In the control group matched for body mass index three sub jects refused and two were excluded because of catheter problems due to difficulties in catheterization of the ra dial artery. In the lean control group three subjects were excluded, two because of catheter problems and one subject refused catheterization. Eleven subjects with positive family histories of hypertension, 10 matched controls, and 11 lean controls with negative family histo ries were subjected to intraarterial pressure recordings and sodium excretion measurements during acute saline infusion. 36
37
STUDY PROTOCOL The protocol was approved by the Ethics committee of the Faculty of Medicine, University of Göteborg, and informed consent was obtained from all subjects prior to the investigations. On the investigational day, the subjects attended the laboratory at the Department of Clinical Physiology, Sahlgrenska Hospital. All subjects were instructed to adhere to their ordinary life style and avoid changes in food intake, alcohol consumption and exercise prior to the investigation. Before the experimental procedure all subjects underwent a routine physical examination and on two occasions one week apart, supine blood pres sures were measured in both arms. One week after the last blood pressure measurements the subjects attended the research unit for the investigational procedures be tween 08:00 and noon, in a sound-proof room at an ambient temperature between 22 and 24 °C.
STUDY GROUPS
METHODS
Normotensive healthy young men matched for age (mean age 36 ± 5 years) with positive (n = 15) and negative (n = 29) family histories of hypertension were recruited for the study. The control group was divided into one group matched for body mass index (n = 15) to those with positive family histories, and a second lean control group (n = 14) with negative family histories of hypertension and normal body mass index. All subjects included in the study were sons of fathers who had participated in the Primary Preventive Study in Göte borg. All young men with positive family histories of hypertension had a hypertensive father who had been
Intraarterial Blood Pressure and Heart Rate Intraarte rial blood pressure was measured via a polyethylene catheter inserted into the brachial or radial artery of the left arm. After catheterization and 60 min of supine rest, blood pressure was recorded with a pressure transducer (Statham P-23, Gould Statham, Cleveland OH) with the zero level at midchest position. The arterial pressure transducer was calibrated against a standard mercury manometer. Intraarterial mean blood pressure was ob tained from electrically damped curves. Saline infusion was performed by administration of 1000 mL body-tempered (36.6°C) 0.9% saline solution
35
Downloaded from http://ajh.oxfordjournals.org/ at The University of British Colombia Library on October 14, 2015
family histories of hypertension and genetically predis posed to primary hypertension are at higher risk of de veloping elevated blood pressure. Moreover, further attention has been drawn to the possibility that genetic predisposition may interact with renal sodium han dling and that an environmental factor such as sodium intake might influence blood pressure. During longterm sodium loading, subjects with positive family histo ries of hypertension increased more in blood pres sure, as compared with subjects with negative fam ily histories of hypertension. In young normotensive subjects with positive family histories of hypertension, semichronic sodium load increased cardiac output without changing blood pressure. The renal sodium handling of a sodium load is mark edly influenced by the prevailing sodium balance, renal function, the renin-angiotensin-aldosterone sys tem, atrial natriuretic peptide, and renal artery pressure. Renal sympathetic nerve activity has also been shown to be of importance for the renal sodium handling in both experimental and human stud ies. In subjects with positive family histories of hyper tension there is a relationship between increased sympa thetic nerve activity and enhanced proximal tubular sodium reabsorbtion. Moreover, the blunted natriure sis seen in such individuals is associated with higher renin levels. In an effort to provide some explanation to these and other potential pathophysiologic mechanisms in pri mary hypertension, different abnormalities of mem brane sodium transport have been characterized in iso lated blood c e l l s . Similar changes in sodium membrane transport have also been reported in normo tensive subjects with positive family histories of hyper tension, suggested to be related to a reduction in the ouabain-sensitive component of cellular sodium ef flux. The present study was initiated in order to inves tigate if normotensive subjects with positive family his tories of hypertension disclose an altered renal sodium handling and an abnormal blood pressure response to a rapid saline load during habitual sodium intake.
571
572
AJH-JULY
WIDGREN ET A L
(155 mmol/L NaCl) as fast as possible into the right antecubital vein. In all subjects the infusion was ended within 10 min. Heart rate was calculated from simulta neously recorded electrocardiograms.
2
2 38
Urine and Plasma Analyses Urine was collected dur ing two consecutive 24-h periods prior to the examina tion day from 07:00 to 07:00 the day after. Sampling was started when the subject had emptied his bladder after night, and was ended with the overnight urine the fol lowing day. The creatinine content was used as an index of completeness of urine collection, which was accepted if creatinine exceeded 8.8 mmol/24 h (1 g ) . Sodium determined by flame photometry is given as the mean sodium excretion during two 24-h collections. During saline loading on the study day urine was voided freely without catheterization approximately 35 min after the infusion was ended. All subjects were reminded to empty their bladder completely and the fractional so dium excretion is given as mmol/min. Blood samples were drawn through a peripheral in dwelling venous catheter, after at least 45 min of supine rest and directly after the saline load had been given. Blood samples for noradrenaline were collected in chilled ( ± 0 ° ) glass tubes containing Na -EDTA and glutathion on ice water, immediately cold-centrifuged (3000 rpm) at + 4 ° , and frozen at - 7 0 ° C until analysis. Plasma noradrenaline in venous blood was analyzed using high-performance liquid chromatography with electrochemical detection. Plasma renin activity was determined using a radioimmunoassay (RIA) method for angiotensin I . Blood samples were collected in icecold tubes containing Na -EDTA, and plasma was dialyzed before incubation to eliminate previously gener ated angiotensin I and angiotensinase effectively. An giotensin II was analyzed on 5 mL plasma samples by RIA and blood samples were collected in ice-cold tubes containing Na -EDTA and O-phenatroline for inhibi tion of converting enzyme and angiotensinases and then centrifuged at + 4 ° within 10 min. Serum aldoster one was determined using a commercially available ra dioimmunoassay kit (International CIS, France). 39
4, NO. 7, PART 1
erythrocytes were incubated for 15, 60, 120, and 240 min in presence of N a and the uptake could be de scribed as a monoexponential function. This monoexpo22
kt
nential uptake (Y) can be written as Υ = Ε + ^ (1— e~ ), - 1
1
where m denotes influx (mmol X L X h ), k = the rate constant of cellular efflux (h" ), and Ε = the rapid initial uptake of N a (mmol X L" ), which in erythrocytes is close to zero. Estimates for m, k, and Ε that make this formula best describe the observed uptake for N a were calculated according to the least square method. For determination of ouabain-sensitive sodium efflux rate constant all samples were preincubated for 15 min in presence of ouabain (0.4 mmol X L " Kemila). The erythrocytes were then washed and added to the final incubation solution also containing ouabain (0.4 mmol X L ) . Total sodium efflux rate constant was deter mined concomitantly by carrying out identical incuba tions in absence of ouabain. The incubation times and calculation of sodium efflux rate constant were carried out in the same way as described before. The ouabainsensitive efflux rate constant was expressed as total ef flux rate constant minus efflux rate constant in presence of ouabain. 1
22
1
22
1
_ 1
43
Plasma and Blood Volume Plasma volume was deter mined and calculated with a I-human serum albumin method. Blood samples were drawn at zero 5, 10, 15, and 20 min after injection. The hypothetical plasma concentration of I at zero time was estimated from a plot of log concentration against time. From that con centration and the originally injected amount of I plasma volume was calculated. 125
1 2 5
1 2 5
2
40
41
2
42
2
Determination of Ouabain-Sensitive Efflux Rate Constant The rate of sodium efflux was calculated from uptake values of N a in erythrocytes during steady state conditions by using a modified Kenye's for mula, as previously described in detail. The washed 22
43
Statistical Methods For the statistical analyses stan dard methods were used for calculation of mean, stan dard deviations (SD), and 95% confidence intervals. Differences within groups at different times were as sessed using a paired t test. Only two-tailed tests were used, and Ρ ^ .05 was regarded as statistically signifi cant. One-way analyses of variance were used to test the hypothesis of no difference in means between thé three groups. Correlation analyses between different vari ables were obtained assuming linear regression and handled by Stat view 5 1 2 + in a Macintosh computer (Apple, Cuppertino, CA). RESULTS Intraarterial Blood Pressure and Heart Rate In sub jects with positive family histories of hypertension both systolic and diastolic blood pressures were significantly higher ( 1 4 1 ± 1 2 / 7 2 ± 9 mm Hg) as well as in controls matched for body mass index (140 ± 1 2 / 7 3 ± 10 mm Hg) (P < .05, respectively) as compared with subjects in the lean control group with negative family histories of hypertension (129 ± 1 3 / 6 4 ± 7 mm Hg). Heart rate at baseline was similar in the three groups (Table 1).
Downloaded from http://ajh.oxfordjournals.org/ at The University of British Colombia Library on October 14, 2015
Body Weight and Body Mass Index Body weight was measured with subjects lightly dressed and using a level balance to the nearest 0.5 kg. Body height was measured without shoes and to the nearest 0.5 cm. Body mass index was calculated as body weight (kg) / body height (m ). Body surface area was calculated as (body weight [kg] + (body height [cm] - 160))/100 +
1991-VOL.
AJH-JULY
1991-VOL.
4, NO. 7, PART 1
RENAL SODIUM HANDLING AND FAMILY HISTORIES OF HYPERTENSION
573
TABLE 1. BLOOD PRESSURE, BASELINE DATA AND HORMONAL EFFECTS OF ACUTE INTRAVENOUS SALINE LOAD IN SUBJECTS WITH POSITIVE FAMILY HISTORIES OF HYPERTENSION (PFH) AND CONTROLS MATCHED FOR BODY MASS INDEX AND NEGATIVE FAMILY HISTORIES OF HYPERTENSION (NFHO), AND LEAN CONTROLS WITH NORMAL BODY MASS INDEX AND NEGATIVE FAMILY HISTORIES OF HYPERTENSION (NFHN) Ρ PFH η = 11 Mean
2
Sodium efflux rate constant ( h ) Plasma renin activity - 1
(ng/mL/h) Angiotensin II ( n g / m L ) Plasma v o l u m e (L) Blood v o l u m e (L) Plasma n o r a d r e n a l i n e (ng/mL) Baseline After 1 0 0 0 m L N a C l Serum aldosterone (nmol/L) Baseline After 1 0 0 0 m L N a C l
141 72
SD
12
Mean
NFHN η = 11 SD
Mean
SD
PFH
PFH
V
V
Ό
NFHO
NFHN
NFHN
NFHO
140
12
129
13
NS
1991;
4:570-578
Bengt Κ Widgren, Hans Herlitz, Thomas Hedner, Goran Berglund, John Wikstrand, Olof Jonsson, and Ove K. Andersson
The natriuretic and intra-arterial blood pressure re sponse to an acute saline load (1000 mL 0.9% NaCl), was studied in normotensive young men with posi tive (n = 11) and negative (n = 21) family histories of hypertension. The age-matched (36 ± 5 years) control group with negative family histories of hy pertension was subdivided into two groups, one matched for body mass index (BMI) to the subjects with positive family histories of hypertension (n = 10), and another lean control group (n = 11). Baseline blood pressure was significantly higher in subjects with positive family histories of hyper tension and in controls matched for BMI as com pared with lean controls. Sodium excretion in creased in all three groups during the saline infusion, while subjects with positive family histo ries of hypertension disclosed a diminished na triuretic response as compared with the two control groups. Systolic blood pressure increased signifi cantly during the saline load in subjects with positive family histories of hypertension, while
A
reduced intrinsic ability of the kidney to ex crete sodium and water has been suggested to be an inherited pathogenetic factor in pri mary hypertension. Lever et al, on the other 1
2
From the Department of Medicine, Hypertension Unit (BRW, HH, GB, OKA), Department of Clinical Pharmacology (TH), the Wallen berg Laboratory for Cardiovascular Research (JW), and the Depart ment of Surgery (OJ), Sahlgrenska Hospital, University of Gothen burg, Göteborg, Sweden. Prof. G. Berglund is now with the Department of Medicine, Malmö General Hospital, University of Lund, Malmö, Sweden. Address correspondance and reprint requests to Bengt R. Widgren, Department of Medicine, Hypertension Unit, Sahlgrenska Hospital, S-413 45 Göteborg, Sweden.
© 1991 by the American Journal of Hypertension, Inc.
in subjects with negative family histories of hyper tension, no significant change in blood pressure was observed. Plasma renin activity, angiotensin II, serum aldosterone, plasma noradrenaline, blood volume, and ouabain-sensitive erythrocyte sodium efflux rate constant did not differ between the three groups at baseline. A significant negative correlation was found between baseline sodium ex cretion and sodium efflux rate constant in subjects with positive family histories of hypertension. We conclude that the subjects with positive fam ily histories of hypertension exhibit a blunted na triuretic and an exaggerated blood pressure re sponse to an acute saline load as compared with the two control groups with negative family histories of hypertension. This could be of neuronal and/or hormonal origin. Am J Hypertens 1991;4:570-578 KEY WORDS: Family history of hypertension, renal sodium excretion, pressor response, sympathetic ac tivity, sodium efflux rate constant.
hand, proposed that hypertensive patients are charac terized by an abnormal sodium handling which was not due to a primary renal disturbance but rather to a lesion as a consequence of the hypertension. However, in sev eral studies patients with primary hypertension have responded to intravenous saline infusion with a more pronounced natriuresis than that in normotensive sub jects. The pathophysiologic basis for this response is not clear but a high blood pressure and low renin seems to be a prerequisite. In contrast, in hypertensives with normal renin a blunted natriuresis to saline load was reported. Substantial evidence exists that subjects with positive 3
4
5
0895-7061/91/$3.50
Downloaded from http://ajh.oxfordjournals.org/ at The University of British Colombia Library on October 14, 2015
Blunted Renal Sodium Excretion During Acute Saline Loading in Normotensive Men With Positive Family Histories of Hypertension
AJH-JULY
1991-VOL
4, NO. 7, PART 1
RENAL SODIUM HANDLING AND FAMILY HISTORIES OF HYPERTENSION
6-9
10
11
12,13
14
15
16
17
18,19
20
21-24
25
10
26-28
29-31
32,33
34
followed for many years at our outpatient hypertension unit. These hypertensive fathers had both of their par ents treated for hypertension or had a history of stroke before the age of 65 years. The control group with nega tive family histories of hypertension were recruited from the same study cohort among the sons of normo tensive fathers without family histories of hypertension or stroke. Selection procedures and cardiovascular characteristics of the parents of the examined young men have been described in detail elsewhere. In the group with positive family histories of hyper tension four subjects refused catheterization. In the control group matched for body mass index three sub jects refused and two were excluded because of catheter problems due to difficulties in catheterization of the ra dial artery. In the lean control group three subjects were excluded, two because of catheter problems and one subject refused catheterization. Eleven subjects with positive family histories of hypertension, 10 matched controls, and 11 lean controls with negative family histo ries were subjected to intraarterial pressure recordings and sodium excretion measurements during acute saline infusion. 36
37
STUDY PROTOCOL The protocol was approved by the Ethics committee of the Faculty of Medicine, University of Göteborg, and informed consent was obtained from all subjects prior to the investigations. On the investigational day, the subjects attended the laboratory at the Department of Clinical Physiology, Sahlgrenska Hospital. All subjects were instructed to adhere to their ordinary life style and avoid changes in food intake, alcohol consumption and exercise prior to the investigation. Before the experimental procedure all subjects underwent a routine physical examination and on two occasions one week apart, supine blood pres sures were measured in both arms. One week after the last blood pressure measurements the subjects attended the research unit for the investigational procedures be tween 08:00 and noon, in a sound-proof room at an ambient temperature between 22 and 24 °C.
STUDY GROUPS
METHODS
Normotensive healthy young men matched for age (mean age 36 ± 5 years) with positive (n = 15) and negative (n = 29) family histories of hypertension were recruited for the study. The control group was divided into one group matched for body mass index (n = 15) to those with positive family histories, and a second lean control group (n = 14) with negative family histories of hypertension and normal body mass index. All subjects included in the study were sons of fathers who had participated in the Primary Preventive Study in Göte borg. All young men with positive family histories of hypertension had a hypertensive father who had been
Intraarterial Blood Pressure and Heart Rate Intraarte rial blood pressure was measured via a polyethylene catheter inserted into the brachial or radial artery of the left arm. After catheterization and 60 min of supine rest, blood pressure was recorded with a pressure transducer (Statham P-23, Gould Statham, Cleveland OH) with the zero level at midchest position. The arterial pressure transducer was calibrated against a standard mercury manometer. Intraarterial mean blood pressure was ob tained from electrically damped curves. Saline infusion was performed by administration of 1000 mL body-tempered (36.6°C) 0.9% saline solution
35
Downloaded from http://ajh.oxfordjournals.org/ at The University of British Colombia Library on October 14, 2015
family histories of hypertension and genetically predis posed to primary hypertension are at higher risk of de veloping elevated blood pressure. Moreover, further attention has been drawn to the possibility that genetic predisposition may interact with renal sodium han dling and that an environmental factor such as sodium intake might influence blood pressure. During longterm sodium loading, subjects with positive family histo ries of hypertension increased more in blood pres sure, as compared with subjects with negative fam ily histories of hypertension. In young normotensive subjects with positive family histories of hypertension, semichronic sodium load increased cardiac output without changing blood pressure. The renal sodium handling of a sodium load is mark edly influenced by the prevailing sodium balance, renal function, the renin-angiotensin-aldosterone sys tem, atrial natriuretic peptide, and renal artery pressure. Renal sympathetic nerve activity has also been shown to be of importance for the renal sodium handling in both experimental and human stud ies. In subjects with positive family histories of hyper tension there is a relationship between increased sympa thetic nerve activity and enhanced proximal tubular sodium reabsorbtion. Moreover, the blunted natriure sis seen in such individuals is associated with higher renin levels. In an effort to provide some explanation to these and other potential pathophysiologic mechanisms in pri mary hypertension, different abnormalities of mem brane sodium transport have been characterized in iso lated blood c e l l s . Similar changes in sodium membrane transport have also been reported in normo tensive subjects with positive family histories of hyper tension, suggested to be related to a reduction in the ouabain-sensitive component of cellular sodium ef flux. The present study was initiated in order to inves tigate if normotensive subjects with positive family his tories of hypertension disclose an altered renal sodium handling and an abnormal blood pressure response to a rapid saline load during habitual sodium intake.
571
572
AJH-JULY
WIDGREN ET A L
(155 mmol/L NaCl) as fast as possible into the right antecubital vein. In all subjects the infusion was ended within 10 min. Heart rate was calculated from simulta neously recorded electrocardiograms.
2
2 38
Urine and Plasma Analyses Urine was collected dur ing two consecutive 24-h periods prior to the examina tion day from 07:00 to 07:00 the day after. Sampling was started when the subject had emptied his bladder after night, and was ended with the overnight urine the fol lowing day. The creatinine content was used as an index of completeness of urine collection, which was accepted if creatinine exceeded 8.8 mmol/24 h (1 g ) . Sodium determined by flame photometry is given as the mean sodium excretion during two 24-h collections. During saline loading on the study day urine was voided freely without catheterization approximately 35 min after the infusion was ended. All subjects were reminded to empty their bladder completely and the fractional so dium excretion is given as mmol/min. Blood samples were drawn through a peripheral in dwelling venous catheter, after at least 45 min of supine rest and directly after the saline load had been given. Blood samples for noradrenaline were collected in chilled ( ± 0 ° ) glass tubes containing Na -EDTA and glutathion on ice water, immediately cold-centrifuged (3000 rpm) at + 4 ° , and frozen at - 7 0 ° C until analysis. Plasma noradrenaline in venous blood was analyzed using high-performance liquid chromatography with electrochemical detection. Plasma renin activity was determined using a radioimmunoassay (RIA) method for angiotensin I . Blood samples were collected in icecold tubes containing Na -EDTA, and plasma was dialyzed before incubation to eliminate previously gener ated angiotensin I and angiotensinase effectively. An giotensin II was analyzed on 5 mL plasma samples by RIA and blood samples were collected in ice-cold tubes containing Na -EDTA and O-phenatroline for inhibi tion of converting enzyme and angiotensinases and then centrifuged at + 4 ° within 10 min. Serum aldoster one was determined using a commercially available ra dioimmunoassay kit (International CIS, France). 39
4, NO. 7, PART 1
erythrocytes were incubated for 15, 60, 120, and 240 min in presence of N a and the uptake could be de scribed as a monoexponential function. This monoexpo22
kt
nential uptake (Y) can be written as Υ = Ε + ^ (1— e~ ), - 1
1
where m denotes influx (mmol X L X h ), k = the rate constant of cellular efflux (h" ), and Ε = the rapid initial uptake of N a (mmol X L" ), which in erythrocytes is close to zero. Estimates for m, k, and Ε that make this formula best describe the observed uptake for N a were calculated according to the least square method. For determination of ouabain-sensitive sodium efflux rate constant all samples were preincubated for 15 min in presence of ouabain (0.4 mmol X L " Kemila). The erythrocytes were then washed and added to the final incubation solution also containing ouabain (0.4 mmol X L ) . Total sodium efflux rate constant was deter mined concomitantly by carrying out identical incuba tions in absence of ouabain. The incubation times and calculation of sodium efflux rate constant were carried out in the same way as described before. The ouabainsensitive efflux rate constant was expressed as total ef flux rate constant minus efflux rate constant in presence of ouabain. 1
22
1
22
1
_ 1
43
Plasma and Blood Volume Plasma volume was deter mined and calculated with a I-human serum albumin method. Blood samples were drawn at zero 5, 10, 15, and 20 min after injection. The hypothetical plasma concentration of I at zero time was estimated from a plot of log concentration against time. From that con centration and the originally injected amount of I plasma volume was calculated. 125
1 2 5
1 2 5
2
40
41
2
42
2
Determination of Ouabain-Sensitive Efflux Rate Constant The rate of sodium efflux was calculated from uptake values of N a in erythrocytes during steady state conditions by using a modified Kenye's for mula, as previously described in detail. The washed 22
43
Statistical Methods For the statistical analyses stan dard methods were used for calculation of mean, stan dard deviations (SD), and 95% confidence intervals. Differences within groups at different times were as sessed using a paired t test. Only two-tailed tests were used, and Ρ ^ .05 was regarded as statistically signifi cant. One-way analyses of variance were used to test the hypothesis of no difference in means between thé three groups. Correlation analyses between different vari ables were obtained assuming linear regression and handled by Stat view 5 1 2 + in a Macintosh computer (Apple, Cuppertino, CA). RESULTS Intraarterial Blood Pressure and Heart Rate In sub jects with positive family histories of hypertension both systolic and diastolic blood pressures were significantly higher ( 1 4 1 ± 1 2 / 7 2 ± 9 mm Hg) as well as in controls matched for body mass index (140 ± 1 2 / 7 3 ± 10 mm Hg) (P < .05, respectively) as compared with subjects in the lean control group with negative family histories of hypertension (129 ± 1 3 / 6 4 ± 7 mm Hg). Heart rate at baseline was similar in the three groups (Table 1).
Downloaded from http://ajh.oxfordjournals.org/ at The University of British Colombia Library on October 14, 2015
Body Weight and Body Mass Index Body weight was measured with subjects lightly dressed and using a level balance to the nearest 0.5 kg. Body height was measured without shoes and to the nearest 0.5 cm. Body mass index was calculated as body weight (kg) / body height (m ). Body surface area was calculated as (body weight [kg] + (body height [cm] - 160))/100 +
1991-VOL.
AJH-JULY
1991-VOL.
4, NO. 7, PART 1
RENAL SODIUM HANDLING AND FAMILY HISTORIES OF HYPERTENSION
573
TABLE 1. BLOOD PRESSURE, BASELINE DATA AND HORMONAL EFFECTS OF ACUTE INTRAVENOUS SALINE LOAD IN SUBJECTS WITH POSITIVE FAMILY HISTORIES OF HYPERTENSION (PFH) AND CONTROLS MATCHED FOR BODY MASS INDEX AND NEGATIVE FAMILY HISTORIES OF HYPERTENSION (NFHO), AND LEAN CONTROLS WITH NORMAL BODY MASS INDEX AND NEGATIVE FAMILY HISTORIES OF HYPERTENSION (NFHN) Ρ PFH η = 11 Mean
2
Sodium efflux rate constant ( h ) Plasma renin activity - 1
(ng/mL/h) Angiotensin II ( n g / m L ) Plasma v o l u m e (L) Blood v o l u m e (L) Plasma n o r a d r e n a l i n e (ng/mL) Baseline After 1 0 0 0 m L N a C l Serum aldosterone (nmol/L) Baseline After 1 0 0 0 m L N a C l
141 72
SD
12
Mean
NFHN η = 11 SD
Mean
SD
PFH
PFH
V
V
Ό
NFHO
NFHN
NFHN
NFHO
140
12
129
13
NS
