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Br J Pharmacol. 1995 Jul;115(6):889-94.

Substance P-induced relaxation and hyperpolarization in human cerebral arteries.

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1
Department of Neurology, Malmö General Hospital, Sweden.

Abstract

1. Vascular effects of substance P were studied in human isolated pial arteries removed from 14 patients undergoing cerebral cortical resection. 2. Substance P induced a concentration-dependent relaxation in the presence of indomethacin. No relaxation was seen in arteries where the endothelium had been removed. 3. N omega-nitro-L-arginine (L-NOARG, 0.3 mM) abolished the relaxation in arteries from six patients. The relaxation was only partially inhibited in the remaining eight patients, the reduction of the maximum relaxation being less than 50% in each patient. 4. The L-NOARG-resistant relaxation was abolished when the external K+ concentration was raised above 30 mM. 5. Substance P caused a smooth muscle hyperpolarization (in the presence of L-NOARG and indomethacin), but only when the artery showed an L-NOARG-resistant relaxation. 6. The results indicate that nitric oxide is an important mediator of endothelium-dependent relaxation in human cerebral arteries. Furthermore, another endothelium-dependent pathway, causing hyperpolarization and vasodilatation, was identified in arteries from more than half the population of patients.

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