Relation between Cyclic GMP Generation and Cerebrovascular Reactivity: Modulation by NPY and α‐Trinositol

Abstract

It is considered that cyclic guanosine monophosphate (cGMP) plays a pivotal role in mediating the relaxation of vascular and nonvascular smooth muscles. cGMP steady state levels are regulated by guanylyl cyclase, cGMP phosphodiesterases and its flux from cells. The present study examines the possible relation between cerebrovascular vasodilator agents and generation of cGMP in guinea pig cerebral vessels. Acetylcholine, substance P, nitroglycerine and sodium nitroprusside significantly increased the generation of cGMP. The application of acetylcholine, substance P, nitroglycerine and sodium nitroprusside elicited concentration-dependent relaxation of basilar artery segments. Neuropeptide Y increased the generation of cGMP by 2%-46% of control levels (at 10(-7)-10(-6)M of neuropeptide Y; *P < 0.05). In addition, neuropeptide Y (10(-6)M) induced a transient relaxation of the precontracted guinea pig basilar arteries with endothelium. This transient relaxation was blocked by nitro-L-arginine (10(-4)M). alpha-Trinositol does not alter the formation of cGMP nor the neuropeptide Y-induced relaxation. In the presence of alpha-trinositol neuropeptide Y (10(-7)-10(-6)M) did not significantly elevate the production of cGMP as compared with controls. The rise in cGMP induced by acetylcholine, substance P and nitroglycerine was slightly increased by the addition of neuropeptide Y (3 x 10(-7) M). Acetylcholine and substance P induced an endothelium-dependent relaxation of the precontracted guinea pig basilar arteries, while sodium nitroprusside and nitroglycerine induced an endothelium-independent relaxation. Acetylcholine, substance P and nitroglycerine induced concentration-dependent relaxations of basilar artery, respectively. The relaxation elicited by acetylcholine or substance P, but not nitroglycerine, was markedly attenuated by neuropeptide Y (3 x 10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Vasodilation in human subcutaneous arteries induced by neuropeptide Y is mediated by neuropeptide Y Y1 receptors and is nitric oxide dependent

“…When the subcutaneous vessels were pretreated with the nitric oxide synthetase inhibitor, L-NAME, the dilatory response was almost completely abolished, indicating that the dilation was nitric oxide dependent. This result is in accordance with an in vivo study in feline cerebral arteries and an in vitro study on guinea pig basilar arteries (Kobari et al 1993;You et al 1995).…”

Impaired vasodilator response to organic nitrates in isolated basilar arteries

“…In accordance, another investigation with guinea‐pig basilar arteries obtained similar results. Vasorelaxation experiments demonstrated a poor activity of GTN, while endothelium‐dependent vasodilation was normal ( You et al ., 1995 ). The maximal vasodilator response to GTN (100 μ M ) was approximately 50% of maximal vasodilation.…”

Blockade of nitric oxide decreases the renal vasodilatory effect of neuropeptide Y in the insulin-treated diabetic rat

“…The present study indicates that the previous observations may be explained by NPY having a vasodilatory effect which, in diabetic rats, seems to be dependent on NO. In guinea-pig basilar arteries [47] and in human subcutaneous vessels [48], NPY may induce an endothelium-dependent relaxation mediated via NO. The latter effect led us to speculate if α-trinositol may somehow act via a NO-dependent mechanism.…”