Angiotensin II and renal medullary blood flow in Lyon rats.
The present study evaluated the acute effects of ANG II (5-480 ng/kg iv) and phenylephrine (PE; 0.2-146 microg/kg iv) on total renal (RBF) and medullary blood flow (MBF) in anesthetized Lyon hypertensive (LH) and low-blood-pressure (LL) rats. ANG II and PE induced dose-dependent decreases in both RBF and MBF, which were greater in LH than in LL rats. Interestingly, after ANG II, but not after PE, the initial medullary vasoconstriction was followed by a long-lasting and dose-dependent vasodilation that was significantly blunted in LH compared with LL rats. The mechanisms of the MBF effects of ANG II were studied in LL rats only. Blockade of AT(1) receptors with losartan (10 mg/kg) abolished all the effects of ANG II, whereas AT(2) receptor blockade with PD-123319 (50 microg x kg(-1) x min(-1) iv) did not change these effects. Indomethacin (5 mg/kg) decreased by approximately 90% the medullary vasodilation induced by the lowest doses of ANG II (from 15 ng/kg). In contrast, N(G)-nitro-l-arginine methyl ester (10 mg/kg and 0.1 mg. kg(-1). min(-1) iv) and the bradykinin B(2)-receptor antagonist HOE-140 (20 microg/kg and 10 microg x kg(-1) x min(-1) iv) markedly lowered the medullary vasodilation at the highest doses of ANG II only. In conclusion, this study shows that LH rats exhibit an altered MBF response to ANG II compared with LL rats and indicates that the AT(1) receptor-mediated medullary vasodilator response to low doses of ANG II is mainly due to the release of PGs, whereas the dilator response to high doses of ANG II has additional nitric oxide- and kinin-dependent components.
Sarkis
Albert
A
Unité Mixte de Recherche 5014, Centre National de la Recherche Scientifique, Institut Fédératif de Recherche Cardio-vasculaire 39, Faculté de Pharmacie, 69373 Lyon cedex 08, France. sarkisalbert@hotmail.com
Liu
Kiao Ling
KL
Lo
Ming
M
Benzoni
Daniel
D
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007679:Kidney Medulla / Q000098:blood supply*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000502:physiology; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D009569:Nitric Oxide; C065679:icatibant; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin