saralasin and Constriction--Pathologic

Glomerular circulatory dynamics were assessed in 60 adult anesthetized rats, which were either deprived or not deprived of water for 24-48 h. Water-deprived rats (n = 21) were characterized by a depressed level of single nephron glomerular filtration rate (SNGFR) when compared with nonwater-deprived controls (n = 8) (23.2 +/- 1.3 vs. 44.8 +/- 4.1 nl/min). This was primarily due to decreased glomerular plasma flow rate (71 +/- 5 vs. 169 +/- 23 nl/min) and glomerular capillary ultrafiltration coefficient (0.028 +/- 0.003 vs. 0.087 +/- 0.011 nl/[s . mmHg]). Infusion of saralasin to these water-deprived rats resulted in significant increases in plasma flow rate and ultrafiltration coefficient, and decline in arteriolar resistances. Consequently, SNGFR increased by approximately 50% from pre-saralasin levels. When water-deprived saralasin-treated rats were given a specific antagonist to the vascular action of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP, a fall in systemic blood pressure occurred, on average from 102 +/- 5 to 80 +/- 5 mmHg, unaccompanied by dilation of renal arterioles, so that both plasma flow rate (129 +/- 8 vs. 85 +/- 13 nl/min) and SNGFR (31.0 +/- 2.9 vs. 18.2 +/- 4.4 nl/min) decreased. This more selective extrarenal constrictor action of AVP was further documented in additional studies in which cardiac output and whole kidney blood flow rate were simultaneously measured. In water-diuretic rats, administration of a moderately pressor dose of AVP (4 mU/kg per min) resulted in a significant rise in kidney blood flow rate (from 8.8 +/- 1.2 to 9.6 +/- 1.3 ml/min). The higher kidney blood flow rate occurred despite a fall in cardiac output (from 111 +/- 7 to 98 +/- 9 ml/min), and was associated with a significant increase in the ratio of systemic vascular to renal vascular resistance (on average from 0.083 +/- 0.014 to 0.106 +/- 0.019). Furthermore, infusion of d(CH2)5Tyr(Me)AVP to water-deprived animals (n = 6) to antagonize endogenous AVP resulted in systemic but not renal vasodilation, so that kidney blood flow rate fell (by approximately 30%), as did systemic-to-renal resistance ratio (by approximately 30%). When the above two experiments were repeated in indomethacin-treated animals, exogenous AVP administration in water-diuretic rats (n = 6) and antagonism of endogenous AVP in water-deprived rats (n = 7) caused, respectively, parallel constriction and dilation in systemic and renal vasculatures. The net effect was unaltered systemic to r

Topics: Animals; Arginine Vasopressin; Constriction, Pathologic; Extracellular Space; Glomerular Filtration Rate; Hemodynamics; Indomethacin; Kidney Glomerulus; Male; Microcirculation; Perfusion; Prostaglandins; Rats; Rats, Inbred Strains; Saralasin; Water Deprivation

The increase in arterial pressure and vascular resistance during acute unilateral renal artery stenosis (RSt) in conscious rats is, in part, dependent on elevated neurogenic vascular tone produced by an indirect neural interaction of angiotensin II (ANG II) with the sympathetic nervous system. The present experiments examined whether this interaction occurs within the central nervous system. Conscious rats that had been chronically instrumented with miniaturized Doppler flow probes for measurement of regional vascular resistance were subjected to a 50% reduction in unilateral renal flow with an implanted pneumatic occluder. Arterial pressure increased by 35% after 60 min of RSt. In animals in which the pressor response to intracerebroventricular (icv) ANG II had been eliminated by prior surgical interruption of the "ANG II pressor pathway" in the anterior hypothalamus, the increase in blood pressure following RSt was attenuated by 44% (P less than 0.01). In a second series, a central action of ANG II during acute renal hypertension (RH) was assessed by central ANG II receptor blockade with icv saralasin. Unlike normotensive controls, acutely RH animals responded to saralasin with significant (P less than 0.01) decreases in arterial pressure (-32%) and hindquarters (-26%) and contralateral renal (-9%) resistance. These changes were accentuated (-57% decrease in pressure) in animals made areflexic by prior sinoaortic baroreceptor denervation. Thus activation of the sympathetic nervous system during the early high-renin phase of RH depends significantly on a central action of ANG II. This mechanism may account for some 40-50% of the pressure increase following acute RSt.

Topics: Afferent Pathways; Angiotensin II; Animals; Carotid Sinus; Central Nervous System; Consciousness; Constriction, Pathologic; Hypertension, Renal; Hypothalamus; Male; Nerve Block; Pressoreceptors; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Reflex; Renal Artery Obstruction; Saralasin

Intravascular coagulation in the rat kidney was induced by intravenous infusion of thrombin for 1 hr. The proximal tubular free-flow (Pt) and stop-flow (Psf) pressures were measured by micropuncture. Some proximal tubules were obstructed with solid paraffin before infusion of thrombin. In certain rats saralasin or indomethacin was administered for 1 hr starting 30 min after the thrombin infusion, and the effect on the tubular pressures was studied. The deposition of fibrin in the glomeruli was examined by light and electron microscopy. Pt fell from 15 +/- 1 (SE) to 7 +/- 2 mm Hg (P less than 0.05) during the infusion of thrombin. After a brief period of increased pressure the Psf fell rapidly from 37 +/- 1 to 17 +/- 1 mm Hg (P less than 0.05). In the previously obstructed nephrons the pressure (Po) increased parallel to the increase in Psf but remained elevated after the infusion of thrombin, 54 +/- 2 mm Hg. The arterial blood pressure (Pa) increased from 119 +/- 2 to 138 +/- 3 mm Hg (P less than 0.05). Saralasin raised the Psf from 15 +/- 1 to 19 +/- 1 mm Hg (P less than 0.05) but had no effect on Pt, Po, or Pa. Indomethacin did not influence the pressures. Morphological examination revealed fibrin in all glomeruli of normal nephrons. In the previously obstructed nephrons the deposition of fibrin was almost totally prevented. The results suggest that glomerular filtration is important for deposition of fibrin in the kidney.

Topics: Animals; Blood Coagulation; Constriction, Pathologic; Fibrin; Indomethacin; Kidney; Kidney Glomerulus; Kidney Tubules; Male; Pressure; Rats; Rats, Inbred Strains; Saralasin; Thrombin