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Am J Physiol Regul Integr Comp Physiol 273: R1793-R1799, 1997;
0363-6119/97 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 5 1793-R1799, Copyright © 1997 by American Physiological Society

ARTICLES

Pivotal role of the renin-angiotensin system in Lyon hypertensive rats

P. Lantelme, M. Lo, L. Luttenauer and J. Sassard
Departement de Physiologie et de Pharmacologie Clinique, Centre National de la Recherche Scientifique, Faculte de Pharmacie, Lyon, France.

We assessed the role of the renin-angiotensin system (RAS) in Lyon genetically hypertensive (LH) and normotensive (LN) rats by measuring 1) kidney renin and prorenin contents; 2) effects of early, prolonged angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and regional hemodynamics; and 3) acute and chronic responses to angiotensin II (ANG II) and norepinephrine (NE). At the adult age, LH rats differed from LN rats by elevated BP, left ventricle weight, and vascular resistances, especially in the kidneys, associated with lower kidney renin and prorenin contents. ACE inhibition (perindopril, 3 mg.kg-1.24 h-1 orally from 3 to 15 wk of age) suppressed the development of hypertension, cardiac hypertrophy, and the increase in renal vascular resistances. No specific hypersensitivity to ANG II could be disclosed in acute conditions. In perindopril-treated LH rats, a 4-wk infusion of ANG II (200 ng.kg-1.min-1) but not of NE (1,000 ng.kg-1.min-1) restored hypertension, mimicked the hemodynamic alterations seen in untreated LH rats, and produced a brief sodium retention. It is concluded that in LH rats, despite a low basal renin secretion, hypertension and hemodynamic abnormalities 1) are fully dependent on an active RAS and 2) may involve an enhanced sensitivity to the chronic effects of ANG II.


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