VASOCONSTRICTOR RESPONSES TO COMPONENTS OF THE RENIN‐ANGIOTENSIN SYSTEM IN CYCLOSPORIN‐INDUCED HYPERTENSION IN THE RAT

1. Since plasma renin activity is increased in cyclosporin A (CsA)‐induced hypertension in the rat, the role of the vascular renin‐angiotensin system (RAS) in CsA‐induced hypertension was investigated in rat mesenteric resistance vessels. 2. Female Wistar rats received CsA (10 mg/kg per day, s.c.) or vehicle for 30 days. CsA treatment increased tail‐cuff systolic blood pressure (CsA treated 135 ± 3 mmHg vs control 125 ± 1 mmHg, P<0.0001). 3. Mesenteric resistance arteries (200–300 μm) were isolated and mounted in a microvessel myograph. Concentration‐response curves to tetradecapeptide renin substrate (10‐¹¹‐10⁻⁶ mol/L), angiotensin I (10‐^l1‐10⁻⁶ mol/L) and angiotensin II (10‐¹²‐10⁻⁶ mol/L) showed no differences between CsA‐treated and control groups. 4. Mesenteric vascular angiotensin‐converting enzyme (ACE) characteristics were determined by radioligand binding. There were no differences in the content or affinity of ACE between CsA‐treated and control rats. 5. These results suggest that the mesenteric vascular RAS does not play a major role in CsA‐induced hypertension in the rat.