Role of sensory nervous system vasoactive peptides in hypertension.
The goal of the present research was to elucidate the roles and mechanisms by which the sensory nervous system, through the actions of potent vasodilator neuropeptides, regulates cardiovascular function in both the normal state and in the pathophysiology of hypertension. The animal models of acquired hypertension studied were deoxycorticosterone-salt (DOC-salt), subtotal nephrectomy-salt (SN-salt), and Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertension during pregnancy in rats. The genetic model was the spontaneously hypertensive rat (SHR). Calcitonin gene-related peptide (CGRP) and substance P (SP) are potent vasodilating neuropeptides. In the acquired models of hypertension, CGRP and SP play compensatory roles to buffer the blood pressure (BP) increase. Their synthesis and release are increased in the DOC-salt model but not in the SN-salt model. This suggests that the mechanism by which both models lower BP in SN-salt rats is by increased vascular sensitivity. CGRP functions in a similar manner in the L-NAME model. In the SHR, synthesis of CGRP and SP is decreased. This could contribute to the BP elevation in this model. The CGRP gene knockout mouse has increased baseline mean arterial pressure. The long-term synthesis and release of CGRP is increased by nerve growth factor, bradykinin, and prostaglandins and is decreased by alpha2-adrenoreceptor agonists and glucocorticoids. In several animal models, sensory nervous system vasoactive peptides play a role in chronic BP elevation. In the acquired models, they play a compensatory role. In the genetic model, their decreased levels may contribute to the elevated BP. The roles of CGRP and SP in human hypertension are yet to be clarified.
Watson
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Clinical Center, Michigan State University, East Lansing, MI 48824-1315, USA. ralph.watson@ht.msu.edu
Supowit
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Zhao
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Katki
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Dipette
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*
D013373:Substance P; D003900:Desoxycorticosterone; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester