Augmented Vascular Response of the Nephrectomized Rat to Angiotensin

Abstract

It has been shown that nephrectomized animals, in general, are more reactive to angiotensin and renin than are control animals ( 1,2 ) . Potentiation of the responses has been noted not to appear until some hours postnephrectomy ( 3 -5 ) . Also, lower base line blood pressures have been noted in nephrectomized rats some hours postnephrectomy ( 5 ) .Pressor responses in dogs have been shown to be somewhat related to serum K levels. For instance, insulin administration to lower serum K in normal dogs decreased pressor responsiveness. The insulin effects were reversed by KCl administration. A corollary was the finding that hypokalemia induced by peritoneal dialysis in a nephrectomized dog decreased vascular responsiveness to pressors. Nephrectomized dogs with hyperkalemia showed increased responsiveness to pressors In view of the above findings, studies were undertaken to determine if there was any correlation between pressor responsiveness and serum K changes in bilaterally ureterally ligated or nephrectomized rats at a time postoperatively when the experimental groups showed increased sensitivity to intravenous angiotensin injections.Method. The rats used for the following experiments were males and weighed 2 80-3 80 g. The rats were designated as follows: M = mock operated, N = bilateral nephrectomy and UL = bilateral ureteral ligation. All operations were carried out using ether anesthesia. The mock operation consisted of exposing both kidneys by retroperitoneal incisions followed by appropriate suturing. In addition, some M rats were etherized but not operated. All animals were kept fasting after the operative procedures until the time of the (6)-sensitivity experiments or until measurement of serum Na and K.At the time of the sensitivity experiments (2-20 hr postoperatively), the rats were anesthetized with Nembutal ( 3 3 mg/kg). The blood pressure was obtained from the carotid artery via pressure transducer recording on a Grass polygraph. The jugular vein was used for the site of injections. The injections consisted of saline followed by different doses of angiotensin I1 followed again by injections of saline. The peak pressure responses were measured. The responses to saline injection alone, if any, were then subtracted from the responses to angiotensin 11.The plasma ion studires were carried out separately from the sensitivity studies on different groups of animals but the operative manipulations were the same as those used for the rats in the sensitivity experiments. There were 5 rats used in each group at different hours postoperatively. Plasma Na and K were measured by standard flame photometry techniques.The angiotensins used in these experiments were: (a) naturally occurring hog angiotensin II,l and (b) synthetic angiotensin I1 amide (5-valyl aspartyl amide angiotensin 11) purchased from Ciba.

Mechanism of adrenal angiotensin II receptor changes after nephrectomy in rats.

“…It therefore seems possible that an alternative explanation, such as the change in ionic composition of plasma, might be responsible for the observed receptor changes after nephrectomy. Nephrectomized rats have a rise of serum potassium of 3 meq as early as 10-12 h after nephrectomy (6). In addition, we have suggested that potassium acts directly on the adrenal glomerulosa during dietary K+-loading to increase angiotensin II receptors (7).…”