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

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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 10−7‐10−6M of neuropeptide Y; *P−6M) induced a transient relaxation of the precontracted guinea pig basilar arteries with endothelium. This transient relaxation was blocked by nitro‐L‐arginine (10−4M). α‐Trinositol does not alter the formation of cGMP nor the neuropeptide Y‐induced relaxation. In the presence of α‐trinositol neuropeptide Y (10−7‐10−6M) 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 (3×10−7M). 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 (3×10−7M). This inhibitory effect of NPY on vasomotor responses was completely reversed by α‐trinositol (10−6M).
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