β-adrenergic antagonists influence abdominal aorta contractility by mechanisms not involving β-adrenergic receptors.
β-adrenergic receptors (β-AR) are widely distributed in the cardiovascular system, where they considerably contribute to the control of its functions. β-blockers are commonly used in the treatment of disorders of the circulatory system. They act primarily by inhibiting cardiac β-receptors. However, there are also reports of pleiotropic action of β-blockers as well as of new compounds created to study β3 adrenergic receptors. The study aimed to investigate additional mechanisms of action of β-AR inhibitors in the rabbit abdominal aorta with emphasis on their action on α-adrenergic receptors and calcium influx. Responses to propranolol, betaxolol, metoprolol and SR59230A were evaluated in phenylephrine and PGF(2alpha) precontracted aortic rings. The effect of propranolol on the phenylephrine concentration-contraction curve was examined. Propranolol (≥ 10 μM) and SR59230A (≥ 0.1 μM) induced relaxations in phenylephrine-precontracted rings, while betaxolol and metoprolol had little effect. The β-AR inhibitors produced further contraction of tissues preincubated with PGF(2alpha), excluding SR59230A, which after initial contraction, elicited marked relaxation at a concentration above 1 ĕM. 100 μM of propranolol caused a significant rightward shift of the concentration-contraction curve to phenylephrine with no reduction in the maximum response. Incubation of aortic rings in phentolamine reduced the maximal contraction to propranolol; verapamil pretreatment by contrast enhanced contractile response. In conclusion, SR59230A and propranolol most probably act as α1-AR competitive antagonists in the presence of phenylephrine in rabbit abdominal aortic rings. After α-ARs blockade, propranolol exerts a weak relaxing activity connected with Ca2+ channel inactivation. SR59230A at a high concentration acts on the rabbit aorta by an additional mechanism needing further investigation.
Willy
W
Hauzer
Jolanta
J
Bujok
Albert
A
Czerski
Agnieszka
A
Rusiecka
Ewa
E
Pecka
Jan
J
Gnus
Wojciech
W
Zawadzki
Wojciech
W
Witkiewicz
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D011433:Propranolol; D015237:Dinoprost; D014700:Verapamil; D010646:Phentolamine