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).
Dhein
S
S
Institut für Pharmakologie, Universität zu Köln, Federal Republic of Germany.
Titzer
S
S
Wallstein
M
M
Müller
A
A
Gerwin
R
R
Panzner
B
B
Klaus
W
W
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