Aldosterone is well known to increase renal collecting duct ENaC expression and activity thereby contributing to sodium retention and hypertension. The ENaC is also expressed in vascular smooth muscle and endothelial cells. Aldosterone has been shown to elicit vascular actions such as accelerated ageing and endothelial dysfunction. Cyp1a1ren-2 transgenic rats carry a renin transgene the expression of which can be induced by feeding an inductor. During transgene induction, these rats show high plasma aldosterone and tissue angiotensin II levels. We tested if hypertension in Cyp1a1ren-2 transgenic rats is sensitive to amiloride and if transgene activation causes amiloride-sensitive alterations in artery function that may contribute to hypertension.

Cyp1a1ren-2 transgenic rats (n = 6–8 per group) were randomized to control (ctr), three weeks transgene induction (ind) and three-weeks transgene induction + amiloride (amil) during the last week. At the end of the experiment, mean arterial pressure (MAP) was 118 2 (ctr), 153 8 (ind) and 118 2 mmHg (amil). Amiloride-induced arterial pressure reduction in transgen-induced rats was accompanied by increased natriuresis. With MAP as effective transmural pressure, third order mesenteric and intrarenal arteries did not show differences in lumen diameter, vascular compliance, a₁-adrenoceptor- or depolarisation-induced vasoconstriction. In vivo intrarenal artery acetylcholine administrations (maximum dose 70 ng) which were without significant effects on systemic arterial pressure caused a rise in renal blood flow to 130% of control values in both transgene-induced and control animals.

We conclude that amiloride effectively reduces arterial pressure in Cyp1a1ren-2 transgenic rats likely by stimulating renal sodium excretion but without appreciable effects on small artery function. Endothelial dysfunction of the renal vasculature is not a pathogenetic factor in hypertension development in these rats.