Vasodilator effect of tertatolol in isolated perfused rat kidneys: involvement of endothelial 5-HT1A receptors.
The aim of the studies was to examine the mechanism of the renal vasodilator action of the beta-adrenoceptor antagonist tertatolol. In isolated Tyrode perfused rat kidneys, constricted with norepinephrine, serotonin (5-HT) or BaCl2, tertatolol evokes dilatations; these vasodilator responses are not due to an interaction of tertatolol with alpha- or beta-adrenoceptors, muscarinic or nicotinic receptors, opioid receptors, dopamine or histamine receptors and they are independent of prostaglandin release. In the presence of ritanserin and ICS 205930, to block 5-HT2 and 5-HT3 receptors, tertatolol, 5-HT, 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) all evoked renal vasodilator responses that were significantly reduced by the nonselective 5-HT antagonist metergoline and by the selective 5-HT1A antagonist BMY 7378 suggesting that 5-HT1 receptors resembling the 5-HT1A subtype were involved. The nitric oxide (NO) inhibitors hemoglobin and nitro-L-arginine (L-NNA), as well as the guanylate cyclase inhibitor methylene blue also inhibited the vasodilator responses to tertatolol and to the serotonergic agonists, suggesting the involvement of the NO-cyclic GMP pathway. These data suggest that 5-HT receptors located on the vascular endothelium of the rat renal circulation are involved in the vasodilator responses caused by tertatolol and these receptors resemble the 5-HT1A subtype.
Verbeuren
T J
TJ
Division of Angiology Institut de Recherche Servier Suresnes France.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000737:chemistry*; D008297:Male; D010477:Perfusion; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012077:Renal Artery / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D013876:Thiophenes; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011985:Receptors, Serotonin; D013876:Thiophenes; D014665:Vasodilator Agents; C005632:tertatolol