Intravenous Angiotensin II Research Articles

The role of the subfornical organ in drinking induced by angiotension in the Japanese quail, Coturnix coturnix japonica.

Synthetic 5-valine angiotensin II (AII) induced copious drinking when applied directly to the the subfornical organ (SFO) in the Japanese quail. Reliable response was obtained with as little as 1 ng of AII. The amount of water intake increased dose-dependently from 5 ng to 1 microgram. A latent period of 73.0 +/- 11.0 seconds at 100 ng was noted. The electrical destruction of the SFO significantly reduced the amount of water intake induced by both intravenous and intracranial AII injections. The decrease was proportional to the extent of the SFO lesion. It is conceivable, therefore, that the SFO plays an important role in elicitation of drinking by AII in birds as suggested in mammals.

Antidiuretic hormone release and the pressor response to central angiotensin II and cholinergic stimulation

Intraventricular (IVT) injections of angiotensin II (AII) have been shown to produce a short latency blood pressure increase and antidiuretic hormone (ADH) release in several species of mammals. In addition, IVT injections produce these same responses in the rat. Unanaesthetized hydrated rats have been used as their own bioassay to study if the pressor effect produced by IVT AII is caused by the vasopressin release. The results indicate that intraventricular injections of AII in a dose range of 0.5–500 ng result in dose dependent ADH release of from 0.04 to 3.32 mU, and carbachol in doses from 0.025 ng to 250 ng produces ADH release from 0.29 to 4.01 mU. Intravenous AII or carbachol in the same dose range did not release ADH in detectable amounts. The time course and magnitude of ADH release produced by intraventricular AII or carbachol injections and data from hypophysectomized rats indicates that vasopressin is partially but not totally responsible for the centrally-induced blood pressure increase. The data suggest that central activation of the sympathetic nervous system is also involved in the response. To test this, 11 rats received peripheral sympathectomy with 6-hydroxydopamine. The amount of ADH released to a central All challenge in these animals was not changed. Following sympathectomy, there was an increased sensitivity to vasopressin which could completely account for the pressor responses observed.

Autoregulation of renal blood flow in the puppy.

The ability of the immature kidney to autoregulate blood flow was investigated. Renal blood flow was measured by electromagnetic flowmeter. In six puppies, selective blockade of the intrarenal effects of angiotensin II (AII) by [1-sarcosine, 8-alanine]angiotensin II (anti-AII) administered into the renal artery did not change renal blood flow. During selective renal AII blockade, intravenous AII raised perfusion pressure from 76 +/- 2 to 100 +/- 6 mmHg. Renal blood flow increased from 1.59 +/- 0.29 to 1.98 +/- 0.59 ml/g kidney per min, but returned to control levels within 40 s in spite of persistent arterial pressure elevation. In another group of seven puppies, renal blood flow remained constant despite reduction of renal perfusion pressure by aortic constriction to 60 mmHg. In two of these seven puppies intrarenal anti-AII did not abolish autoregulation. Autoregulation of renal blood flow occurs in the puppy and is not influenced by inhibition of angiotensin. The renin-angiotensin system does not appear to be involved in the normal regulation of renal blood flow in the puppy.

Effect of angiotensin II on renal water excretion.

In the present study the effect of angiotensin II (AII) on renal water excretion was evaluated. In dogs undergoing a water diuresis, neither the intravenous (IV) (40ng/kg per min) nor intracarotid (5-10 ng/kg per min) infusion of AII significantly altered urinary osmolality (Uosm) or free-water clearance (CH2O). Intravenous infusion of a competitive inhibitor of AII (1-sarcosine,8-glycine AII) into hydropenic dogs also failed to alter Uosm and CH2O significantly. To examine whether AII might suppress, rather than stimulate, vasopressin release, AII was also infused into hydropenic animals. No effect on Uosm and CH2O was observed during the intracarotid infusion. A significant fall in Uosm and rise in CH2O occurred during the intravenous AII infusion, but reversal after cessation of the infusion was incomplete and statistically not significant. Some suppression of antidiuretic hormone (ADH) release during the intravenous infusion of AII, however, was suggested since no similar alteration in renal water excretion was observed during an intravenous AII infusion in hypophysectomized animals receiving a constant infusion of ADH. Taken together, the present results provide no evidence for a direct effect of AII to alter ADH release or to interfere with the peripheral action of ADH. Suppression of ADH release may sometimes occur with pressor doses of intravenous angiotensin, but this effect is clearly less consistent than previously observed with intravenous norepinephrine.

Renal hypertension in rats immunized against angiotensin I and angiotensin II.

Rats, actively immunized against angiotensin I (AI) and angiotensin II (AII), were subjected to unilateral renal artery constriction to determine whether the resulting hypertension, which may still ensue in the animal immunized against AII, could be prevented by such combined immunity. Sustained immunity to both AI and AII neither changed preoperative blood pressures of the rats from those of control mock-immunized rats nor altered the incidence or severity of renal dip hypertension. Vascular hyperresponsiveness to small quantities of free angiotensin could not be invoked to explain the hypertension, for there was no significant difference between mock-immunized hypertensive animals, and those remaining normotensive, regarding pressor sensitivity to intravenous AI, AII, renin, and norepinephrine. (AI + AII)-immunized hypertensive rats required AI doses averaging 260 times greater than nonimmune hypertensives to elicit equipressor responses, and were refractory to renin, but not to norepinephrine. Thus, while previous studies have not excluded direct participation of endogenous AI in renal clip hypertension in rats, evidence from our experiments makes it extremely difficult to sustain any pressor function therein for circulating AI or AII. Our results also preclude involvement of AII produced from circulating AI by conversion within arteriolar walls, close to receptor sites, since AI immunity would block this mechanism of action.