Effects of pinacidil on the sympatho-adrenal system in dogs.
1. The aim of the present work was to study the antihypertensive effect of pinacidil, a potassium channel opener, in sinoaortic denervated (SAD) conscious dogs and to investigate whether the involvement of the sympathetic nervous system induced by this vasodilator compound is only of baroceptor reflex origin. 2. Pinacidil (0.1, 0.2, 0.4 mg kg-1 i.v.) induced a dose-dependent decrease in blood pressure in normal as well as in SAD dogs. In contrast, the induced-tachycardia observed in normal dogs was not found in SAD animals. 3. Since pinacidil induced an increase in plasma catecholamines, free fatty acids, glucose, plasma renin activity and aldosterone in SAD dogs it is suggested that this sympathetic activation is independent of the baroreceptor reflex pathways. 4. The sympathetic activation is mainly of peripheral origin, since pinacidil (0.7 mg kg-1 i.v.) induced an increase in adrenaline release from the adrenal gland after section of the great splanchnic nerve in anaesthetized dogs. This increase is probably due to an effect that does not involve K+ channel opening. However, this effect of pinacidil was not observed during splanchnic nerve stimulation (in this case, the involvement of K+ channel opening is suggested).
Damase-Michel
C
C
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U 317, Faculté de Médecine, Toulouse, France.
Tran
M A
MA
Montastruc
J L
JL
Moatti
J P
JP
Montastruc
P
P
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000758:Anesthesia; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D020110:Pinacidil; D012083:Renin / Q000097:blood; D012849:Sinoatrial Node / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*
D001786:Blood Glucose; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D006146:Guanidines; D000450:Aldosterone; D020110:Pinacidil; D012083:Renin