Acta physiol. scand. 1975. 95. 318-328 From the Institute of Physiology, University of Bergen, Norway
Effect of Vasoactive Agents on the Distribution of Renal Cortical Blood Flow in Dogs BY I. TYSSEBOTN and A.
KIRKEB~
Received 2 May 1975
Abstract TYSSEBOTN, I. and A. KIRKEBB. Effect of vasoactive agents on the distribution of renal cortical blood flow in dogs. Acta physiol. scand. 1975. 95. 318-228. The distribution of renal cortical blood flow was studied in 6 Nembutal anesthetized dogs during control periods and during infusions of adrenaline, noradrenaline, angiotensin and vasopressin. Local cortical blood flow was measured as H, gas desaturation rate recorded polarographically by platinum electrodes in outer and inner cortex. The total renal blood flow (RBF) was measured by an electromagnetic flow meter. In the control period the outer cortical blood flow (OCF) and inner cortical blood flow (ICF) averaged 3.59 (kS.D. 0.85) ml/min-g and 3.23 (+S.D. 0.64) ml/min*g, respectively. Infusions of the various vasoactive agents caused essentially equal vascular responses. All agents caused increased local renal resistance and reduction of RBF whether given intravenously or intraarterially. The RBF could be lowered to 20-50 % of initial control flow by increasing doses of vasoactive agents. OCF and I C F fell proportionately and almost to the same extent as RBF, or O C F fell slightly more than ICF. There was no evidence for patchy or zonal hypoperfusion in cortex caused by infusion of adrenaline, noradrenaline, angiotensin and vasopressin.
It is well known that adrenaline, noradrenaline, angiotensin and vasopressin increase the vascular resistance in the kidney and decrease total renal blood flow (RBF). However, several investigators have claimed that the resistance is not increased in all parts of the kidney. Thus Trueta et al. (1947) found in rabbits that large doses of adrenaline and vasopressin reduced the amount of Indian ink and angiographic contrast medium reaching the outer cortex, whereas more contrast was found in the juxtamedullary circulation. More recently, Carriere (1969) and Grandchamp, Ayer and Truniger (1971), using external recording of ls3Xe or sKKrwashout, reported that vasopressor infusion caused a marked reduction of flow in outer cortex, whereas flow in the juxtamedullary cortex and outer medulla remained unchanged or even increased. However, this evidence of a preferential vasoconstriction in the outer cortex has not been confirmed by measurements of microsphere distribution (Rector et al. 1972) and local heat clearance (Grangsjo and Persson 1971). In view of these conflicting results we have reinvestigated the question of the distribution of blood flow in the cortex during the renal vasoconstriction produced by several vasoactive agents, using the Ha washout method which permits repeatable local blood flow measurements.
318
RENAL CORTICAL BLOOD FLOW
319
too 0
R BF, rnl l m i n
200 100
0
CBF, m 1 l r n l n . g
Fig. 1. Effect of noradrenaline (NA) and angiotensin total renal (Ang) infusion o n arterial pressure (D), blood flow (RBF) and local cortical blood flow (CBF) at 6 different electrode sites in one dog. Open circles: Inner cortex. Closed circles: Outer cortex.
I 0
60
120 rnin
Methods The effect of adrenaline (A), noradrenaline (NA), angiotensin (Ang) (Hypertensin, CIBA) and vasopressin (ADH) (Pitressin, Parke, Davis & Co.) on renal blood flow was determined in 9 expts. on 6 mongrel dogs of both sexes, weighing 15-21 kg. The animals had free access to water and food until 12 h prior to the experiments. The food consisted of fish and pellets providing about 5 g NaC1/24 h. Anesthesia was induced by i.v. injection of Nembutal, 25 mg/kg b.wt. Additional doses of 3 mg/kg were given when needed. Polyethylene catheters were placed in a brachial vein, a brachial and a saphenous artery for infusions and arterial pressure (AP) recording. The kidney was exposed retroperitoneally through a flank incision. An electromagnetic flowmeter probe (Nycotron) was placed o n the renal artery for continuous measurement of total renal blood flow (RBF). Calibration of the flowmeter was performed on the femoral artery. A polyvinyl catheter was inserted in the renal artery with the tip directed upstream. A Blalock clamp was placed on the aorta above the renal arteries to control the renal arterial pressure during the infusion of vasoconstrictor agents. Three L-shaped platinum electrodes were placed in the outer cortex with the sensitive electrode tips 1 4 mm deep, and 3 other electrodes 5-8 mm deep in the inner cortex. The shafts of the electrodes were fixed to the renal capsule by 2 sutures and the electrodes carefully covered with perirenal fat and the wound closed by towel clips. Hydrogen concentration in the tissue around the sensitive electrode tip was determined polarographically at a polarization potential of +0.2 V versus an Ag/AgCI electrode placed subcutaneously on the hip (Aukland et al. 1973). The amplified electrode current was recorded on a 6-channel recorder (Rikadenki Kogyo Co., Model B-64). 3-10 ml saline saturated with hydrogen at 37°C was injected in the renal artery
320
1. TYSSEBOTN AND A. KIRKEB0
TABLE I. OCF/ICF ratio (S.E.) in control periods and during infusion of adrenaline (A), noradrenaline (NA), angiotensin (Ang) and vasopressin (ADH). Agents
Control
Arterial infusion
p, paired t-test*
Control
Venous infusion
p, paired &test*
A n** NA n** Ang n** ADH n**
l.lBf0.09 29 1.05+0.07
1.07&0.05 34 0.92k0.06 29 1.14k0.03 16 1.09k0.06 10
~0.05
l.l0+0.06 12 l.lOk0.03 10 1.2420.04 10 1.26f0.04 10
1.05k0.05 17 1.09k0.04 15 1.29k0.05 20 1.13k0.06 12
Effect of Vasoactive Agents on the Distribution of Renal Cortical Blood Flow in Dogs BY I. TYSSEBOTN and A.
KIRKEB~
Received 2 May 1975
Abstract TYSSEBOTN, I. and A. KIRKEBB. Effect of vasoactive agents on the distribution of renal cortical blood flow in dogs. Acta physiol. scand. 1975. 95. 318-228. The distribution of renal cortical blood flow was studied in 6 Nembutal anesthetized dogs during control periods and during infusions of adrenaline, noradrenaline, angiotensin and vasopressin. Local cortical blood flow was measured as H, gas desaturation rate recorded polarographically by platinum electrodes in outer and inner cortex. The total renal blood flow (RBF) was measured by an electromagnetic flow meter. In the control period the outer cortical blood flow (OCF) and inner cortical blood flow (ICF) averaged 3.59 (kS.D. 0.85) ml/min-g and 3.23 (+S.D. 0.64) ml/min*g, respectively. Infusions of the various vasoactive agents caused essentially equal vascular responses. All agents caused increased local renal resistance and reduction of RBF whether given intravenously or intraarterially. The RBF could be lowered to 20-50 % of initial control flow by increasing doses of vasoactive agents. OCF and I C F fell proportionately and almost to the same extent as RBF, or O C F fell slightly more than ICF. There was no evidence for patchy or zonal hypoperfusion in cortex caused by infusion of adrenaline, noradrenaline, angiotensin and vasopressin.
It is well known that adrenaline, noradrenaline, angiotensin and vasopressin increase the vascular resistance in the kidney and decrease total renal blood flow (RBF). However, several investigators have claimed that the resistance is not increased in all parts of the kidney. Thus Trueta et al. (1947) found in rabbits that large doses of adrenaline and vasopressin reduced the amount of Indian ink and angiographic contrast medium reaching the outer cortex, whereas more contrast was found in the juxtamedullary circulation. More recently, Carriere (1969) and Grandchamp, Ayer and Truniger (1971), using external recording of ls3Xe or sKKrwashout, reported that vasopressor infusion caused a marked reduction of flow in outer cortex, whereas flow in the juxtamedullary cortex and outer medulla remained unchanged or even increased. However, this evidence of a preferential vasoconstriction in the outer cortex has not been confirmed by measurements of microsphere distribution (Rector et al. 1972) and local heat clearance (Grangsjo and Persson 1971). In view of these conflicting results we have reinvestigated the question of the distribution of blood flow in the cortex during the renal vasoconstriction produced by several vasoactive agents, using the Ha washout method which permits repeatable local blood flow measurements.
318
RENAL CORTICAL BLOOD FLOW
319
too 0
R BF, rnl l m i n
200 100
0
CBF, m 1 l r n l n . g
Fig. 1. Effect of noradrenaline (NA) and angiotensin total renal (Ang) infusion o n arterial pressure (D), blood flow (RBF) and local cortical blood flow (CBF) at 6 different electrode sites in one dog. Open circles: Inner cortex. Closed circles: Outer cortex.
I 0
60
120 rnin
Methods The effect of adrenaline (A), noradrenaline (NA), angiotensin (Ang) (Hypertensin, CIBA) and vasopressin (ADH) (Pitressin, Parke, Davis & Co.) on renal blood flow was determined in 9 expts. on 6 mongrel dogs of both sexes, weighing 15-21 kg. The animals had free access to water and food until 12 h prior to the experiments. The food consisted of fish and pellets providing about 5 g NaC1/24 h. Anesthesia was induced by i.v. injection of Nembutal, 25 mg/kg b.wt. Additional doses of 3 mg/kg were given when needed. Polyethylene catheters were placed in a brachial vein, a brachial and a saphenous artery for infusions and arterial pressure (AP) recording. The kidney was exposed retroperitoneally through a flank incision. An electromagnetic flowmeter probe (Nycotron) was placed o n the renal artery for continuous measurement of total renal blood flow (RBF). Calibration of the flowmeter was performed on the femoral artery. A polyvinyl catheter was inserted in the renal artery with the tip directed upstream. A Blalock clamp was placed on the aorta above the renal arteries to control the renal arterial pressure during the infusion of vasoconstrictor agents. Three L-shaped platinum electrodes were placed in the outer cortex with the sensitive electrode tips 1 4 mm deep, and 3 other electrodes 5-8 mm deep in the inner cortex. The shafts of the electrodes were fixed to the renal capsule by 2 sutures and the electrodes carefully covered with perirenal fat and the wound closed by towel clips. Hydrogen concentration in the tissue around the sensitive electrode tip was determined polarographically at a polarization potential of +0.2 V versus an Ag/AgCI electrode placed subcutaneously on the hip (Aukland et al. 1973). The amplified electrode current was recorded on a 6-channel recorder (Rikadenki Kogyo Co., Model B-64). 3-10 ml saline saturated with hydrogen at 37°C was injected in the renal artery
320
1. TYSSEBOTN AND A. KIRKEB0
TABLE I. OCF/ICF ratio (S.E.) in control periods and during infusion of adrenaline (A), noradrenaline (NA), angiotensin (Ang) and vasopressin (ADH). Agents
Control
Arterial infusion
p, paired t-test*
Control
Venous infusion
p, paired &test*
A n** NA n** Ang n** ADH n**
l.lBf0.09 29 1.05+0.07
1.07&0.05 34 0.92k0.06 29 1.14k0.03 16 1.09k0.06 10
~0.05
l.l0+0.06 12 l.lOk0.03 10 1.2420.04 10 1.26f0.04 10
1.05k0.05 17 1.09k0.04 15 1.29k0.05 20 1.13k0.06 12
