PHARMACOLOGICAL EVIDENCE THAT CALCITONIN-GENE-RELATED PEPTIDE IS IMPLICATED IN CEREBRAL AUTOREGULATION

In anesthetized rats, we examined the possibility that calcitonin gene -related peptide (CGRP, a neuropeptide) released in response to transi ent hypotension may contribute to the reflex autoregulation of cerebra l blood flow. Changes in pial arterial diameter (mean 33.0+/-1.1 mu m) with changes in systemic arterial blood pressure (mean 101.9+/-2.7 mm Hg) were observed directly through a closed cranial window. In capsaic in-treated rats (depletor of CGRP and substance P, 50 nmol capsaicin i njected intracisternally 24 h before experiment), vasodilatation, whic h was evoked on transient hypotension, and vasoconstriction on reverse of hypotension were markedly attenuated or almost abolished. When cha nges in pial arterial diameter were plotted as a function of changes i n blood pressure, the slopes of regression lines for vasodilatation an d vasoconstriction were markedly reduced after capsaicin treatment. Si milar reductions were evidenced under suffusion of CGRP antibody serum (1:1,000) and after CGRP receptor desensitization but not after subst ance P receptor desensitization. Pretreatment with glibenclamide, a K-channel antagonist, also caused severe alterations in the autoregulat ory vasomotor responses to hypotension and its reverse. Suffusion with mock cerebrospinal fluid, containing either CGRP or cromakalim, a K+- channel opener, dilated the pial artery in a concentration-dependent m anner, and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was unaffected by glibenclamide. Th us it is suggested that vasodilatation of rat pial arteries in respons e to a transient hypotension is mediated, in part, by the CGRP, which is released from the perivascular sensory fibers, and the vasodilator effect of CGRP may be achieved by an activation of glibenclamide-sensi tive K+ channels.