Renin-angiotensin system in two genetically normotensive strains of Lyon rats.
Compared to the Lyon normotensive (LN) controls, adult Lyon hypertensive rats (LH) exhibit a renin-angiotensin system (RAS) dependent hypertension despite a low renin secretion. This discrepancy could be explained by the elevated slow pressor response to angiotensin II (AII) found in LH rats compared to LN controls. To evaluate more precisely the pathophysiological importance of this increased response, the present work aimed at determining whether the characteristics of the RAS were identical in LN and low blood pressure (LL) rats, the other normotensive control strain simultaneously selected with LH rats. Plasma and kidney renin and prorenin were measured in 11-week-old LN and LL rats. Aortic blood pressure (BP) was recorded at 15 weeks of age in freely moving rats of both strains either untreated or having received an angiotensin converting enzyme inhibitor, perindopril (3 mg/kg/day orally) since the age of 3 weeks. Acute dose-response curves were constructed for AII and norepinephrine (NE). The long-term pressor effects of AII (200 ng/kg/ min) and NE (1000 ng/kg/min) were measured after chronic infusions in perindopril-treated LN and LL rats. LN and LL rats exhibited similar mean BP level before (114 +/- 2 and 117 +/- 2 mm Hg, respectively) and after perindopril treatment (91 +/-3 and 93 +/- 1 mm Hg, respectively). Plasma and kidney renin and prorenin were decreased in LL rats. In acute conditions, LL rats exhibited an unspecific hypersensitivity to AII and NE. Chronically given AII exerted a greater pressor effect in LL than in LN rats after 4 weeks (113 +/- 3 v 97 +/- 5 mm Hg in LL and LN rats respectively, P < .05) and, even more, after 8 weeks of infusion (144 +/- 9 v 124 +/- 4 mm Hg in LL and LN rats respectively, P < .05). The NE was devoid of chronic pressor effects. In conclusion, 1) the increased slow pressor response to AII may not be a critical pathogenetic factor in the development of hypertension, as it also exists in normotensive LL rats; 2) LN and LL rats have the same normal BP despite marked differences in their RAS, thus suggesting that there could be several forms of normotension as known for hypertension; and 3) the simple comparison between one genetically hypertensive strain and one single normotensive control strain does not allow one to conclude that a phenotypic difference is of pathophysiological significance.
Lantelme
P
P
Département de Physiologie et Pharmacologie Clinique, Centre National de la Recherche Scientifique, Unité Propre de Recherche de l'Enseignement Supérieur Associée 5014, Institut Fédératif de Recherche Cardiovasculaire 39, Fa.
Lo
M
M
Sassard
J
J
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D020913:Perindopril / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000097:blood / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D013599:Systole; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000804:Angiotensin II; D012964:Sodium; D012083:Renin; D009638:Norepinephrine; D020913:Perindopril