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 transient hypotension may contribute to the reflex autoregulation of cerebral blood flow. Changes in pial arterial diameter (mean 33.0 +/- 1.1 microns) with changes in systemic arterial blood pressure (mean 101.9 +/- 2.7 mmHg) were observed directly through a closed cranial window. In capsaicin-treated rats (depletor of CGRP and substance P, 50 nmol capsaicin injected intracisternally 24 h before experiment), vasodilatation, which was evoked on transient hypotension, and vasoconstriction on reverse of hypotension were markedly attenuated or almost abolished. When changes in pial arterial diameter were plotted as a function of changes in blood pressure, the slopes of regression lines for vasodilatation and vasoconstriction were markedly reduced after capsaicin treatment. Similar reductions were evidenced under suffusion of CGRP antibody serum (1:1,000) and after CGRP receptor desensitization but not after substance P receptor desensitization. Pretreatment with glibenclamide, a K(+)-channel antagonist, also caused severe alterations in the autoregulatory 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 manner, and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was unaffected by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Hong
K W
KW
Department of Pharmacology, College of Medicine, Pusan National University, Korea.
Pyo
K M
KM
Lee
W S
WS
Yu
S S
SS
Rhim
B Y
BY
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D009479:Neuropeptides; D011758:Pyrroles; D018013:Receptors, Neuropeptide; D014665:Vasodilator Agents; D019806:Cromakalim; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D005905:Glyburide