Cardiovascular effects of calcitonin gene-related peptide in the pithed rat: comparison with substance P.
Recently it has been shown that calcitonin gene-related peptide (CGRP) and substance P (SP) are coexisting in central and peripheral nerve endings of sensory neurons. In the present study we compared the vasodepressor and plasma extravasating activity of CGRP with that of SP. Systemic administration of CGRP to pithed, vagotomized rats evoked a dose dependent, long lasting vasodilation accompanied by a parallel rise in heart rate. The tachycardic response to CGRP may indicate a direct positive chronotropic action on the heart since this effect could not be blocked by beta-adrenoceptor blockade. For any equimolar dose the hypotensive effect of CGRP was much larger than that of SP. Both, CGRP and SP, showed a more pronounced decrease in mean arterial blood pressure after elevation of basal blood pressure levels by constant infusion of either phenylephrine, arginine-vasopressin, or angiotensin II. After systemic administration in equimolar doses CGRP was much less effective in producing plasma extravasation than SP. In conclusion, at equimolar doses CGRP is 10 times more potent than SP in producing vasodilatation but it possesses less than a third of the potency of equimolar doses of SP in producing plasma extravasation.
Haass
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Skofitsch
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D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide; D002199:Capillary Permeability / Q000187:drug effects; D002490:Central Nervous System / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology*
D009419:Nerve Tissue Proteins; D000804:Angiotensin II; D001127:Arginine Vasopressin; D010656:Phenylephrine; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide