Vasopressin modulation of medullary blood flow and pressure-natriuresis-diuresis in the decerebrated rat.

Studies in our laboratory and others have demonstrated that arginine vasopressin (AVP) exerts potent vasoconstrictor actions on the vessels supplying the renal medulla. The physiological importance of these vascular effects of AVP has been difficult to assess because of high endogenous levels of AVP in anesthetized, surgically prepared animals. We have developed a decerebrated, hypophysectomized, renal-denervated rat model that enables us to study the effects of low levels of AVP on the pressure-diuresis, relationship under acute conditions. These rats maintain normal mean arterial pressure (MAP) and plasma AVP (2.5 pg/ml). Cortical and medullary blood flow (CBF and MBF, respectively) were measured by laser-Doppler flowmetry and total renal blood flow (RBF) by transit time flowmetry. Renal interstitial fluid pressure (RIFP) and urinary sodium excretion (UNaV) responses were determined during controlled increases of MAP produced by aortic occlusion below the renal arteries. From a baseline of 97 +/- 2 mmHg, 30% increases in MAP resulted in a 63% increase in MBF, 35% increase in RIFP, and sixfold increase in UNaV, whereas CBF and RBF remained unchanged. Infusion of AVP (0.50 ng.kg-1.min-1, which increased plasma AVP from normal control levels of 3 pg/ml to 11 pg/ml) produced no change in baseline MAP, RBF, or CBF but lowered MBF by 24%, RIFP by 26%, and UNaV by 71%. The slope of the relationship of AP and UNaV, MBF, and RIP was reduced to nearly zero by these small increases of plasma AVP. We conclude that an increase of plasma AVP in the range that occurs with water restriction decreases MBF selectively and greatly attenuates the arterial pressure-MBF and pressure-natriuretic relationship.

Sensitivity of the renal medullary circulation to plasma vasopressin.

Studies were carried out to determine the effects of physiological changes of plasma arginine vasopressin (AVP) on blood flow distribution in the renal cortex and medulla. Acute decerebration was performed so that studies could be carried out within the low physiological range of circulating AVP. Changes of renal cortical and medullary microcirculatory blood flow were measured with implanted optical fibers and laser-Doppler flowmetry, and total renal blood flow was measured with transit-time ultrasonography. During intravenous infusion of increasing doses of AVP, when plasma AVP was increased in steps from 2.9 to 11.2 pg/ml by intravenous infusion, mean arterial pressure (98 +/- 3 mmHg), total renal blood flow (8.2 +/- 0.6 ml. min-1.g kidney-1), and blood flow in the microcirculation of the cortex (2.11 +/- 0.28 V) remained unchanged, whereas that in the renal medulla decreased progressively. Medullary flow was significantly reduced when circulating levels of AVP increased from a control level of 2.8 to 5.0 pg/ml. The reductions of medullary flow were accompanied by parallel increases of urine osmolality. These data indicate that the vessels supplying the renal medullary circulation are sensitive within the range of plasma AVP concentrations observed with moderate water restriction. The medullary circulation exhibits a sensitivity AVP that parallels that found in the medullary collecting ducts.

Renal cortical and medullary blood flow responses during water restriction: role of vasopressin.

Experiments were performed in unanesthetized rats to determine responses to 48 h water restriction of the renal regional microcirculation (cortex, outer medulla, and inner medulla) using implanted optical fibers and laser-Doppler flowmetry. The role of vasopressin (AVP) as a mediator of renal regional blood low changes and its contribution to urinary concentrating ability were assessed by continuous intramedullary interstitial infusion of specific V1 receptor antagonist d(CH2)5 [Tyr-(Me)2, Ala-NH2]AVP (2ng . kg-1 . min-1). Inner medullary blood flow decreased 34% at the end of 48 h of water restriction, whereas cortical and outer medullary flow did not change. This fall in inner medullary blood flow was substantially attenuated (18%) by the continuous interstitial infusion of the antagonist. Plasma AVP levels increased from control levels of 3.4 +/- 1.1 to 20.5 +/- 5.4 pg/ml (P < 0.05) by the end of the 48-h period of water restriction. Arterial pressure increased slightly but significantly during water restriction in the control rats. Infusion of antagonist impaired the maximal urinary concentrating ability, as demonstrated by the lower urine osmolality in this group than in the control group (1,893 +/- 49 vs. 2,419 +/- 225 mosmol/kg H2O; P < 0.05) measured during the second day of water restriction. Sodium and urea concentration decreased 20 and 22%, respectively, indicating that both contributed to the lower urine osmolality observed in the group of rats receiving the antagonist. We conclude that water restriction induces a selective decrease in inner medullary blood flow, which is mediated almost completely by endogenously released AVP. This vascular effect of AVP contributes to the maximum concentrating ability of the kidney.

Physiopathogenesis of acute aortic coarctation hypertension in conscious rats.

We investigated the role of vasopressin, angiotensin II, and catecholamines in the onset of acute (45-minute) aortic coarctation hypertension in conscious rats. Partial aortic constriction was performed by means of a pneumatic cuff placed around the abdominal aorta above the renal arteries for 15 or 45 minutes. A sham-operated group was used as control. Mean carotid pressure before aortic constriction did not differ between rat groups. Aortic constriction produced a similar increase of mean carotid pressure during 15 minutes (36 +/- 3 to 37 +/- 3 mm Hg above basal levels) and 45 minutes (37 +/- 2 to 39 +/- 3 mm Hg). Plasma vasopressin concentration after 15 minutes of coarctation (4.4 +/- 0.5 pg/mL) did not differ from that observed in control rats (3.0 +/- 0.8 pg/mL), whereas after 45 minutes, it was significantly higher (14.3 +/- 3.3 pg/mL). Plasma renin activity increased significantly after coarctation (21.7 +/- 4.1 and 29.9 +/- 2.9 ng angiotensin I/mL per hour, at 15 and 45 minutes, respectively) when compared with control rats (3.9 +/- 0.5 ng angiotensin I/mL per hour). After coarctation, plasma norepinephrine concentration was consistently reduced, whereas plasma epinephrine concentration did not differ from control rats. In conclusion, these data provide evidence for an effective vasopressor role for vasopressin in the genesis of acute (45-minute) aortic coarctation hypertension in conscious rats. In addition, although the results confirm that the renin-angiotensin system participates earlier in the onset of coarctation hypertension, they rule out a significant vasopressor role for catecholamines in the early development of hypertension.