Studies on the role of angiotensin in experimental renovascular hypertension: an immunologic approach

Abstract

A B S T R A C T The role of angiotensin in three forms of experimental hypertension was assessed in rats. First, the acute blood pressure response to injected angiotensin amide and angiotensin acid was determined. Rats made hypertensive with deoxycorticosterone and saline showed exaggerated responses; rats made hypertensive by clipping one renal artery showed depressed responses; and rats made hypertensive by clipping one renal artery and contralateral nephrectomy showed normal responsivity to angiotensin amide but depressed responsivity to angiotensin acid. These findings suggested that different mechanisms may be involved in the three types of hypertension studied.To assess the role of angiotensin in these hypertensive rats the blood pressure response, the presence of antibodies determined by radioimmune techniques, and the degree of refractoriness to injected angiotensin after immunization with angiotensin were studied. None of six rats made hypertensive by deoxycorticosterone and saline, and none of five mock immunized rats with renal hypertension of both types had a fall in blood pressure. By contrast, of the 20 rats with both types of renal hypertension in which antibody determinations were made, 11 had developed a significant antibody titer, of which seven showed a significant reduction in blood pressure at the time of antibody determination, and three of the remaining four had a significant blood pressure reduction earlier in their course. None of the nine renal hypertensive rats without demonstrable antibodies had a reduced blood pressure at the time of antibody determination, and only one had an earlier reduction in This work was presented in part at the 60th Annual Meeting of the American Society for Clinical Investigation, Atlantic City, May 1968 and abstracted in 1968 J. Clin. Invest. 49: 19a, and in 1967 Dr. R. B. Hickler is an Investigator of the Howard Hughes Medical Institute.Received for publication 31 December 1968 and in revised form 28 March 1969. blood pressure. The renal hypertensive rats were all refractory to injected angiotensin after immunization.These results suggest a primary role for angiotensin in both forms of renal hypertension. INTRODUCTIONEvidence for an association between the renin-angiotensin system and the hypertension seen after constriction of a renal artery has been accumulating since 1898 (1-7). The most direct evidence for this association has been the production of antirenin, which results in the neutralization of the pressor effect of injected renin in the assay dog and which is associated with a lowering of the arterial pressure in renal hypertensive dogs,

Pathophysiology of renovascular hypertension.

“…8 Furthermore, removal of the clip or ligature is attended by a prompt return of blood pressure to normal that is paralleled by a reduction in PRA and circulating Ang II. 9 In addition, active or passive immunization to Ang II 10 or the administration of renin inhibitors 1 ' can lower blood pressure in 2K1C chronic severe hypertension. The renin inhibitor CGP-29287 caused declines in blood pressure that could be correlated with basal PRA in one study.…”

Chronic one-kidney hypertension in rabbits. II. Evidence for a new factor.

“…Furthermore, DEAE-cellulose chromatography in a descending pH gradient," employed on an Table I. • The ability of these rabbits to respond to an intravenous prcssor dose of renin while their blood pressure was lowered is presented in Table 4. One Gokiblatt unit (GU) of rabbit renin 1 ' was given via the marginal ear vein. Systolic blood pressures were measured in mm Hg at frequent intervals and were plotted against time in minutes.…”

Renovascular Hypertension in Rats Immunized with Angiotensin II

“…The experimental parallel, i.e., unilateral renal artery constriction with the opposite kidney untouched, produces hypertension in rats, while other experimental animals usually remain normotensive. Christlieb et al (6) found such hypertension alleviated by immunization with angiotensin, but this could not be confirmed by Johnston et al (5). Whatever the reason for the difference in results, both groups started immunization subsequent to the development of hypertension; neither group investigated whether antibody titers were sufficient for the complete inactivation of 150 EIDE injected angiotensin.'…”