Celiprolol exerts microvascular dilatation by activation of beta 2-adrenoceptors.
In order to clarify the question whether the beta 1-selective adrenoceptor antagonist celiprolol possesses vasodilating properties, isolated vascular networks were perfused with increasing concentrations of celiprolol (in a cumulative manner) ranging from 10(-8) to 10(-4) mol/l. The study was carried out using the isolated mesenteric vascular bed of the guinea pig mesenterium coli. Vascular diameters of four different vascular regions [vessels classified as G1 (585 +/- 30 microns), G2 (403 +/- 25 microns), G3 (282 +/- 27 microns) and G4 (197 +/- 13 microns)] were assessed by means of microscopic videoangiometry. Perfusion with celiprolol resulted in concentration dependent vasodilation which was more pronounced in G3 and G4 vessels. In addition, cumulative concentration-response curves were determined from responses obtained in the presence of 10(-8), 10(-7), 10(-6) and 10(-4) mol/l ICI 118,551 (a highly selective adrenoceptor antagonist). In the presence of ICI 118,551 at concentrations greater than or equal to 10(-6) mol/l, no celiprolol response could be observed. Lower concentrations of ICI 118,551 shifted the celiprolol concentration-response curve to the right in a concentration-dependent manner. Therefore, it is concluded (a) that celiprolol has a vasodilating effect, (b) that this vasodilation is produced by stimulation of beta 2-adrenoceptors and (c) that the vasodilating effect is more pronounced in smaller than in larger vessels (G3, G4 vs G1, G2).
Institut für Pharmakologie, Universität zu Köln, Federal Republic of Germany.
S
S
Dhein
S
S
Titzer
M
M
Wallstein
A
A
Müller
R
R
Gerwin
B
B
Panzner
W
W
Klaus
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017272:Celiprolol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects*; D010477:Perfusion; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; C026777:ICI 118551; D017272:Celiprolol