Sensory CGRP depletion by capsaicin exacerbates hypoxia-induced pulmonary hypertension in rats.
Pulmonary hypertension is a debilitating disease that occurs among infants and adults. One of many etiologies is airway hypoxia. We previously demonstrated a role of endogenous calcitonin gene-related peptide (CGRP), a potent vasodilator, in ameliorating the pulmonary vascular pressor response to chronic hypoxia and related changes in the lungs and heart. This study evaluates the role of endogenous sensory CGRP in hypoxic pulmonary hypertension and examines the intrinsic neural microcircuitry. Rats were pretreated with capsaicin i.p. to deplete pulmonary sensory C-fiber stores of CGRP and substance P and placed in hypobaric hypoxia (10% O2, 16 days) or normoxia together with sham controls. Hypoxia increased pulmonary artery pressure, right-ventricular weight, arterial medial thickness, elasticized capillaries, endothelial cell density, lung water and hematocrit in control rats. Capsaicin augmented pulmonary artery pressure and right-ventricular hypertrophy in hypoxia, and medial thickness and endothelial cell density both in normoxia and hypoxia. Because of the limited effects on these parameters by substance P and other capsaicin-sensitive lung agents, our results suggest that sensory CGRP deficit severely exacerbates pathological signs of hypoxic pulmonary hypertension. A neural microcircuitry consistent with an axon reflex pathway is outlined histochemically. We conclude that endogenous CGRP modulates pulmonary vascular tone in hypoxic pulmonary hypertension which requires intact primary sensory fibers.
Tjen-A-Looi
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Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706, USA. keithi@svm.vetmed.wisc.edu
Kraiczi
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Ekman
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Keith
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D000818:Animals; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D015687:Cell Hypoxia; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000209:etiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D010100:Oxygen