Effect of Pinacidil on Sympathetic Neuroeffector Transmission in Rabbit Blood Vessels

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Abstract
The effects of pinacidil on vascular sympathetic neuroeffector transmission were studied. Pinacidil (3 × 10−7‐3 × 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 × 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 × 10−6 M), but not rauwolscine (10−6 M) prevented the enhancement. Pinacidil (10−4 M) did not antagonize the α‐methylnoradrenaline‐induced inhibition of 3H‐overflow evoked by stimulation. Pinacidil (10−5‐3 × 10−5 M) in a non‐competitive manner antagonized the contractions of isolated aorta elicited by noradrenaline (3 × 10−9‐3 × 10−5 M), phenylephrine (2 × 10−8‐3 × 10−4 M), adrenaline (10−9‐3 × 10−5 M), histamine (10−6‐6 × 10−4 M), serotonin (10−8‐10−4 M), and potassium (10−3 M). Pinacidil (10−6‐3 × 10−4 M) and methacholine (3 × 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. Pinacidil (3 × 10−5‐3 × 10−4 M) reduced the accumulation of 3H by aorta incubated with 3H‐NA (10−8 M). It is concluded that pinacidil predominantly is a direct acting vasodilator. Furthermore, pinacidil probably does not inhibit presynaptic inhibitory α2‐adrenoceptors.