Role of the baroreflex in beta 2-sympathomimetic induced tachycardia in male rats.
The aim of the study was to determine whether tachycardia which is associated with the use of beta 2-sympathomimetic tocolytic agents is caused by baroreflex activation or by direct stimulation of cardiac beta-adrenoceptors. In conscious male rats, tachycardiac responses following intravenous injection of hexoprenaline, ritodrine and fenoterol were compared following (i) bilateral sinoaortic denervation (SAD) or (ii) sham-operation, and (iii) ganglionic-blockade using hexamethonium. Dose-ranges were chosen to result in similar reductions in diastolic blood pressure (DAP). Furthermore, following ganglionic blockade, the relative contribution of beta 1-adrenoceptor stimulation was assessed using the selective beta 2-receptor antagonist ICI 118,551. In intact rats, increases in HR induced by all beta-adrenoceptor agonist were comparable. In SAD and ganglion-blocked rats, DAP fell more pronounced at even lower doses. The corresponding increases in HR were approximately 3 times smaller than in intact rats but not different between agents. During ganglionic blockade ICI 118,551 significantly inhibited HR responses to fenoterol and hexoprenaline but not ritodrine. The conclusion is that in intact male rats, baroreflex activation is the major determinant of tachycardia following injection of ritodrine, fenoterol or hexoprenaline. Increasing the beta 2-selectivity of these drugs will not limit the tachycardic effects.
Janssen
B J
BJ
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
van Zijl
J A
JA
Essed
G G
GG
Smits
J F
JF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D003714:Denervation; D005280:Fenoterol / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006594:Hexoprenaline / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012312:Ritodrine / Q000494:pharmacology; D012850:Sinus of Valsalva / Q000294:innervation; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology*; D015149:Tocolytic Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D015149:Tocolytic Agents; D005280:Fenoterol; D018738:Hexamethonium; C026777:ICI 118551; D006594:Hexoprenaline; D012312:Ritodrine