Angiotensin II Receptor Antagonist Losartan Has Persistent Effects on Blood Pressure in the Young Spontaneously Hypertensive Rat: Lack of Relation to Vascular Structure

Abstract

The persistent effects on blood pressure of the angiotensin II receptor antagonist losartan and the converting enzyme inhibitor captopril were compared in the young spontaneously hypertensive rat (SHR). Losartan (DuP753/MK954, 15 mg/kg/day) and captopril (100 mg/kg/day) were given in the drinking water of 3-week-old SHRs for 4- and 10-week durations. Blood pressure was measured during treatment and after treatment was stopped until the age of 30 weeks. Both losartan and captopril given for 4 and 10 weeks prevented the development of hypertension during treatment and redevelopment of hypertension after treatment was stopped. Treatment for 10 weeks was more effective than for 4 weeks in lowering long-term pressure. Four weeks of treatment did not affect the mesenteric resistance artery media/lumen (m₁/l₁) ratio. In contrast, both losartan and captopril given for 10 weeks resulted in large and significant reductions in m₁/l₁ [5.3 ± 0.8 and 5.63 ± 0.8 vs 7.7 ± 0.8 × 10^-2 (SD), p < 0.001]. In losartan-treated rats, plasma renin and angiotensin II concentration were increased between 4- and 7-fold at the end of both treatment periods. These findings show losartan to be an effective antihypertensive agent and support data implicating angiotensin II in the early events leading to hypertension in this model. The abilities of losartan and captopril to affect blood pressure without affecting vascular structure suggest that the latter is a poor predictor of long-term hypertensive levels in the SHR.

Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension.

“…28 If the vasodilator hydralazine is given simultaneously and blood pressure does not rise, this hypertrophic response still occurs, indicating that it is at least in part independent of blood pressure. When spontaneously hypertensive rats are treated with converting enzyme inhibitors 17 ' 29 or angiotensin II antagonists, 18 vascular structure regresses partly but not entirely to normal. In a model of renin-dependent hypertension in the rat, treatment with cilazapril produced complete regression of vascular changes, 30 although this was associated with normalization of blood pressure.…”

“…In both studies there was no evidence of improvement in the functional alterations of resistance arteries of hypertensive patients. In animals such as spontaneously hypertensive rats, treatment with angiotensin I converting enzyme inhibitors 17 or angiotensin II receptor antagonists 18 has been shown to induce some regression of the vascular changes that are characteristic of hypertension in rats, namely, the increased media-lumen ratio and thickened media.…”

Prevention and regression of hypertension: role of renal microvascular protection

“…13,14 Similar studies have been performed by other laboratories using both ACE inhibitors, 15,16 and angiotensin receptor blockers (ARBs). 17,18 In our initial studies, we found that treatment of stroke-prone SHR with an ACE inhibitor from age 3-10 weeks resulted in a sustained suppression of blood pressure, whereas such an effect was not found with the vasodilator hydralazine. 19 Exactly the same results were found with an ARB, suggesting that this effect could be explained by the inhibitory actions of ACE inhibitors and ARB on the RAS.…”

The association of human adipose angiotensinogen gene expression with abdominal fat distribution in obesity

“…14 Rats treated with losartan (angiotensin II receptor antagonist) displayed diminished fat mass and fat cell size. 15 Weight loss was reported as a side effect of angiotensin converting enzyme inhibitors. 16,17 Taken together these data suggest that the angiotensinogen system might be involved in the growth and development of adipose tissue.…”