Differential effects of nebivolol on adrenoceptors in the heart and in resistance arterioles in the rat. Quantitative intravital microscopic analysis.
The effects of adrenoceptor antagonists on heart rate and on arteriolar reactions to epinephrine, terbutaline, vasopressin, angiotensin II or dopamine in the rat cremaster muscle were compared using ECG analysis and quantitative intravital microscopy. Phentolamine (0.5 mg/kg i.v.) significantly reduced the vasoconstriction of arterioles elicited by topically applied epinephrine (10(-8) to 3.3 x 10(-6) M) while propranolol (0.63 mg/kg i.v.) significantly attenuated the arteriolar vasodilatation elicited by topically applied terbutaline (10(-6) to 10(-4) M). Nebivolol (0.63 mg/kg i.v.) at a dose producing a reduction of resting heart rate equivalent to that caused by propranolol modified neither the epinephrine-induced constriction nor the terbutaline-induced vasodilatation of arterioles. The arteriolar vasoconstriction induced by topically applied vasopressin (9.3 x 10(-9) M), angiotensin II (9.4 x 10(-7) M) or dopamine (5.2 x 10(-5) M) was not modified by nebivolol either. While propranolol reduced the tachycardia and hypotension induced by isoprenaline (0.025, 0.1 microgram/kg i.v.), nebivolol reduced the cardiac rhythm increase but not the blood pressure drop in response to the catecholamine (0.025, 0.1, 0.4 micrograms/kg i.v.). The present intravital microscopic study in the rat demonstrated that, at a dose exerting cardiac beta 1-adrenoceptor blockade, nebivolol is devoid of significant activity on alpha 1-, alpha 2-, beta-2-adrenoceptors and on receptors for vasopressin, angiotensin II or dopamine in resistance arterioles.
Loots
W
W
Department of Haematology, Medicinal Chemistry and Pharmacology, Janssen Research Foundation, Beerse, Belgium.
De Clerck
F
F
D000287:Administration, Topical; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001160:Arterioles / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009132:Muscles / Q000098:blood supply; D000068577:Nebivolol; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013726:Terbutaline / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology; D014741:Video Recording
D000322:Adrenergic Agonists; D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D014667:Vasopressins; D000804:Angiotensin II; D011433:Propranolol; D013726:Terbutaline; D004298:Dopamine; D004837:Epinephrine