Effect of tertatolol and of its metabolites and structural analogues in isolated perfused rat kidney vasculature.
The renal vascular effect of tertatolol and analogues was investigated in isolated rat kidney perfused at constant flow in an open circuit with Krebs-Henseleit solution after vascular tone had been reestablished by bolus injections of serotonin or other vasoconstrictor drugs. Against serotonin-induced vasoconstriction, (+/-)tertatolol (3 X 10(-7)-3 X 10(-5) M) evoked concentration-dependent relaxation (IC 50 = 4.6 +/- 0.4 X 10(-6) M), (-)tertatolol was more active than the racemic and (+)tertatolol was less active. (+/-)Tertatolol competitively antagonized serotonin-induced renal constriction (pA2 = 5.6 +/- 0.2). Tertatolol metabolites (4-OH tertatolol, 4,5-di-OH tertatolol, and sulfoxy tertatolol) were inactive. (+/-)Sotalol and (+/-)nadolol, were also inactive in this model and (-)bunolol induced renal vasodilatation only at concentrations 40 times higher than (-)tertatolol. The renal response to tertatolol was not linked to release of prostaglandins or dopamine or to interaction with the dopamine receptor, since neither indomethacin nor SCH 23390 affected tertatolol-induced renal vasodilatation. Tertatolol also elicited relaxation of N6-cyclohexyladenosine-induced renal vasoconstriction (34 +/- 7% relaxation at 3 X 10(-5) M) but was inactive when renal vascular tone was raised by prostaglandin F2 alpha, angiotensin II, or neuropeptide Y in the presence of norepinephrine.
Stephan
D
D
Institut de Pharmacologie, URA DO589 CNRS, Université Louis Pasteur, France.
Barthelmebs
M
M
Krieger
J P
JP
Decker
N
N
Rochat
C
C
Imbs
J L
JL
D000319:Adrenergic beta-Antagonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013876:Thiophenes; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D013876:Thiophenes; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012701:Serotonin; C005632:tertatolol; D007213:Indomethacin