Pivotal role of the renin-angiotensin system in Lyon hypertensive rats.
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.
Lantelme
P
P
Departement de Physiologie et de Pharmacologie Clinique, Centre National de la Recherche Scientifique, Faculté de Pharmacie, Lyon, France.
Lo
M
M
Luttenauer
L
L
Sassard
J
J
D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output; D004792:Enzyme Precursors / Q000378:metabolism; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000201:enzymology; D008297:Male; D020913:Perindopril; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D014655:Vascular Resistance
D000806:Angiotensin-Converting Enzyme Inhibitors; D004792:Enzyme Precursors; D007211:Indoles; D000804:Angiotensin II; D012083:Renin; D020913:Perindopril