Effects of the blockade of the renin-angiotensin system in cyclosporin-induced hypertension.
OBJECTIVE
To compare the acute hypotensive effects of three different methods of inhibiting the renin-angiotensin system in a primate model of cyclosporin-induced hypertension.


METHODS
The effects of maximally effective doses of an angiotensin I converting enzyme inhibitor, antihuman renin antibodies or a renin inhibitor (Ro 42-5892) on arterial pressure were evaluated in cyclosporin-treated monkeys.


METHODS
Squirrel monkeys were made hypertensive by a 4-week treatment with oral cyclosporin (30 mg/kg) and were equipped with a telemetry system in order to measure arterial blood pressure in the conscious state.


RESULTS
Each inhibitor induced a complete suppression of plasma angiotensin II 1 h after administration. The renin antibodies did not decrease blood pressure. Cilazapril decreased blood pressure and Ro 42-5892 was more effective than cilazapril. Moreover, when the renin inhibitor was administered after injection of renin antibodies (rabbit antiserum, 0.4 ml intravenously) or after cilazapril (10 mg/kg orally), it induced a supplementary fall in blood pressure.


CONCLUSIONS
These data demonstrate that in this experimental model of hypertension the three different methods of maximal inhibition of the renin-angiotensin system do not lead acutely to the same blood pressure decrease. The results also suggest that renin inhibition might be more effective than angiotensin converting enzyme inhibition in certain forms of hypertension.
Clozel
J P
JP
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Fischli
W
W
Ménard
J
J
D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D017315:Cilazapril / Q000494:pharmacology*; D016572:Cyclosporine; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008297:Male; D012083:Renin / Q000276:immunology / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012453:Saimiri; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D000906:Antibodies; D017315:Cilazapril; D016572:Cyclosporine; D007093:Imidazoles; D012083:Renin; D000092502:Renin Inhibitors; C065581:remikiren