Effect of perindopril on renal medullary hemodynamics in genetically hypertensive rats.
BACKGROUND
Early and chronic angiotensin converting enzyme (ACE) inhibition prevents hypertension and improves the pressure natriuresis in Lyon hypertensive (LH) rats. The effect of this treatment on the responses of renal medullary blood flow (MBF) to angiotensin II (Ang II) was studied.


METHODS
In chronic experiments, Ang II (7.5 to 480 ng/kg, intravenous) was injected in 15-week-old anesthetized LH and normotensive (LL) control rats treated orally since weaning with perindopril (0.4 or 1.5 mg/kg/day) with or without pretreatment with indomethacin (5 mg/kg intravenous). In acute experiment, Ang II (30 to 480 ng/kg intravenous) was given in LH rats treated acutely with perindopril (1.5 mg/kg, intravenous bolus).


RESULTS
Administration of Ang II induced dose-dependent decreases in MBF, which were greater in LH than in LL rats. In LL rats, the initial and short-lasting (<1 min) medullary vasoconstriction evoked by Ang II was followed by a long-lasting (>2 min) and dose-dependent medullary vasodilation, which was blunted in LH rats. Chronic perindopril treatment normalized the blood pressure level in LH rats and corrected their blunted medullary vasodilation, whereas the same treatment had no significant effect in LL rats. In chronically perindopril-treated LH rats, indomethacin decreased by 90% the medullary vasodilation induced by Ang II. Acute perindopril treatment did not modify the medullary responses to Ang II in LH rats.


CONCLUSIONS
Chronic ACE inhibition restores the vasodilator response of MBF to Ang II in LH rats. This effect, which is not observed after acute inhibition, is mainly mediated through the release of prostaglandins.
Liu
Kiao-Ling
KL
Département de Physiologie et Pharmacologie Clinique, Faculté de Pharmacie, Université Claude Bernard Lyon, 8 avenue Rockefeller, 69373 Lyon Cedex 08, France. klliu@sante.univ-lyon.fr
Lo
Ming
M
Benzoni
Daniel
D
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000235:genetics; D007213:Indomethacin / Q000494:pharmacology; D007679:Kidney Medulla / Q000098:blood supply*; D008297:Male; D020913:Perindopril / Q000494:pharmacology*; D051381:Rats; D011922:Rats, Mutant Strains; D012079:Renal Circulation / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007213:Indomethacin; D020913:Perindopril