On the mechanism of coronary vasodilation induced by angiotensin-(1-7) in the isolated guinea pig heart.
Various mechanisms have been postulated to be involved in angiotensin-(1-7)-induced endothelium-dependent vasodilation. Here, we characterized the vasodilator action of angiotensin-(1-7) in the isolated guinea pig heart. Angiotensin-(1-7) (1-10 nmol, bolus) induced dose-dependent increase in the coronary flow. The coronary vasodilation induced by angiotensin-(1-7) was significantly reduced by the nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME) (100 microM) and abolished by a B(2) receptor antagonist, icatibant (100 nM). Coronary vasodilation induced by bradykinin (3 pmol, bolus) was inhibited by L-NAME and icatibant to similar extent as that induced by angiotensin-(1-7). Neither the selective AT(2) angiotensin receptor antagonist, PD123319 (1 microM), nor the antagonist of a putative angiotensin-(1-7) receptors, [D-alanine-7]-angiotensin-(1-7) (A-779, 1 microM), influenced the response to angiotensin-(1-7). In conclusion, in the isolated guinea pig heart angiotensin-(1-7) induces coronary vasodilation that is mediated by endogenous bradykinin and subsequent stimulation of nitric oxide release through endothelial B(2) receptors. In contrast to other vascular beds, AT(2) angiotensin receptors and specific angiotensin-(1-7) receptors do not appear involved in angiotensin-(1-7)-induced coronary vasodilation in the isolated guinea pig heart.
Kozlovski
Valery I
VI
Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
Lomnicka
Magdalena
M
Fedorowicz
Andrzej
A
Chlopicki
Stefan
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
C092006:7-Ala-angiotensin (1-7); D000319:Adrenergic beta-Antagonists; D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D000804:Angiotensin II; C073402:PD 123319; D009569:Nitric Oxide; C065679:icatibant; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; C118790:angiotensin I (1-7); D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester