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 microns) were isolated and mounted in a microvessel myograph. Concentration-response curves to tetradecapeptide renin substrate (10(-11)-10(-6) mol/L), angiotensin I (10(-11)-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.
Rolls
K A
KA
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Phillips
P A
PA
Aldred
K
K
Hardy
K J
KJ
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000808:Angiotensinogen / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000633:toxicity*; D005260:Female; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D012680:Sensitivity and Specificity; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
C079544:angiotensinogen (1-14); D000808:Angiotensinogen; D000804:Angiotensin II; D016572:Cyclosporine; D000803:Angiotensin I