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)