This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Supowit, S. C. Articles by DiPette, D. J. Search for Related Content PubMed PubMed Citation Articles by Supowit, S. C. Articles by DiPette, D. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines High Blood Pressure Related Collections Other hypertension Gene expression Hypertension - basic studies

(Hypertension. 2001;38:697.)
© 2001 American Heart Association, Inc.

Endocrine Systems

Omapatrilat in Subtotal Nephrectomy-Salt Hypertension

Role of Calcitonin Gene-Related Peptide

Scott C. Supowit; Huawei Zhao; Donna H. Wang; Donald J. DiPette

Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Mich.

Correspondence to Scott C. Supowit, PhD, Michigan State University, 138 Service Rd, B-338 Clinical Center, East Lansing, MI 48824. E-mail scott.supowit{at}ht.msu.edu

Abstract

Abstract—— Calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide, plays a counterregulatory role in subtotal nephrectomy–salt (SN-salt)–induced hypertension, reflecting a stimulation of the efferent vasodilator function of perivascular sensory nerves. To determine the effect of omapatrilat, a dual ACE and neutral endopeptidase inhibitor, on blood pressure and the potential antihypertensive role for CGRP, 24 male Sprague-Dawley rats were separated into 4 groups: (1) SN-salt, (2) SN-salt plus omapatrilat (80 mg · kg^-1 · d^-1 in the drinking water), (3) sham-operated plus salt, (4) sham-operated plus salt and omapatrilat. After 11 days the mean arterial pressure was higher in the SN-salt group (174±10 mm Hg) versus the sham-operated–salt (109±4 mm Hg) and sham-operated–salt plus omapatrilat (105±3 mm Hg) groups. Omapatrilat treatment of the SN-salt rats significantly decreased the mean arterial pressure to 123±7 mm Hg and significantly reduced the heart-to-body weight ratio. Intravenous administration of a specific CGRP receptor antagonist produced a significant 10±2 mm Hg mean arterial pressure increase in the untreated SN-salt hypertensive rats but was without effect in the other groups. This indicates that CGRP does not contribute to the antihypertensive actions of omapatrilat. In addition, CGRP mRNA and protein content in dorsal root ganglia were decreased 25% in the SN-salt plus omapatrilat rats. Thus, omapatrilat not only markedly reduces the blood pressure in this model of renal failure–induced hypertension but may also prevent the abnormal compensatory stimulation of the vasodilator activity of the peripheral sensory nervous system.

Key Words: nervous system • neuropeptides • hypertension, experimental • antihypertensive agents • vasodilator agents

This article has been cited by other articles:

				J. Varagic, D. Susic, M. Slama, and E. D. Frohlich Omapatrilat Induces Profound Renal Vasodilation but Does Not Affect Coronary Hemodynamics Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2003; 8(2): 167 - 174. [Abstract] [PDF]