Effect of pinacidil on sympathetic neuroeffector transmission in rabbit blood vessels.
The effects of pinacidil on vascular sympathetic neuroeffector transmission were studied. Pinacidil (3 x 10(-7)-3 x 10(-4) M) inhibited the contractions of rabbit isolated pulmonary artery evoked by nerve stimulation. This was the case both in the absence and presence of cocaine plus corticosterone. The inhibition reached a steady state and was reversible. Pinacidil (10(-5) -3 x 10(-4) M), in the absence or presence of cocaine plus corticosterone, markedly enhanced the 3H-overflow evoked by electrical-field stimulation of the artery preloaded with 3H-noradrenaline (3H-NA). The enhancement was dependent on frequency (1-30 Hz) in a complex manner. Phentolamine (3 x 10(-6) M), but not rauwolscine (10(-6) M) prevented the enhancement. Pinacidil (10(-4) M) did not antagonize the alpha-methylnoradrenaline-induced inhibition of 3H-overflow evoked by stimulation. Pinacidil (10(-5)-3 x 10(-5) M) in a non-competitive manner antagonized the contractions of isolated aorta elicited by noradrenaline (3 x 10(-9)-3 x 10(-5) M), phenylephrine (2 x 10(-8)-3 x 10(-4) M), adrenaline (10(-9)-3 x 10(-5) M), histamine (10(-6) 6 x 10(-4) M), serotonin (10(-8)-10(-4)M), and potassium (10(-3) M). Pinacidil (10(-6)-3 x 10(-4) M) and methacholine (3 x 10(-8)-10(-6) M) relaxed aorta preconstricted with noradrenaline (10(-7) M). The relaxation caused by pinacidil was not dependent on the presence of endothelial cells, while that seen with methacholine was.(ABSTRACT TRUNCATED AT 250 WORDS)
Nedergaard
O A
OA
Department of Pharmacology, School of Medicine, Odense University, Denmark.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001808:Blood Vessels / Q000294:innervation / Q000378:metabolism; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000294:innervation* / Q000378:metabolism; D009451:Neuroeffector Junction / Q000187:drug effects* / Q000502:physiology; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D011651:Pulmonary Artery / Q000294:innervation / Q000378:metabolism; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D006146:Guanidines; D020110:Pinacidil; D011188:Potassium