5-Hydroxytryptamine-induced vasodilatation in the isolated perfused rat kidney: are endothelial 5-HT1A receptors involved?
Left kidneys obtained from male Wistar rats were perfused with Tyrode solution; the perfusion pressure was measured continuously and taken as an index of vascular resistance in the kidneys. 5-Hydroxytryptamine (5-HT; 3-50 nmol) caused dose-dependent dilator responses in kidneys preconstricted with noradrenaline (0.6 microM) and pretreated with ritanserin (10 nM) and ICS 205930 (10 nM). The 5-HT1 agonist 5-carboxamidotryptamine (5-CT; 16-64 nmol) also caused renal dilatations under similar conditions. The dilator responses to both 5-HT and 5-CT were antagonized by the non-selective 5-HT receptor antagonist metergoline (0.2 microM) and by the selective 5-HT1A receptor antagonist BMY 7378 (0.4 microM). The guanylate cyclase inhibitor methylene blue (30 microM) and the nitric oxide (NO) synthase inhibitor nitro-L-arginine (L-NNA; 100 microM) significantly attenuated the dilator responses to 5-HT and 5-CT. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5-16 nmol) also caused dose-dependent dilator responses in preconstricted rat kidneys. These responses were antagonized by metergoline and BMY 7378 and significantly attenuated by the NO inhibitors hemoglobin (10 microM) and L-NNA. The renal dilator responses noted with the beta-adrenoceptor blocker tertatolol (1-32 nmol) were also antagonized by metergoline and BMY 7378 and significantly reduced by L-NNA and hemoglobin. Both 8-OH-DPAT and tertatolol (1-30 microM) significantly reduced the vasoconstrictor responses to angiotensin II (20 pmol). Our data indicate that 5-HT receptors located on the vascular endothelium of the renal circulation are involved in the dilator actions of 5-HT, 5-CT, 8-OH-DPAT and tertatolol, and suggest that these receptors resemble the 5-HT1A subtype.
Verbeuren
T J
TJ
Institut de Recherches Servier, Department of Angiology, Suresnes, France.
Mennecier
P
P
Laubie
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D010879:Piperazines; D011412:Propanolamines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D000804:Angiotensin II; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D009320:Atrial Natriuretic Factor; C047087:5-carboxamidotryptamine; C005632:tertatolol; D010208:Papaverine; D005996:Nitroglycerin; C053428:BMY 7378; D000109:Acetylcholine