Document Detail


Omapatrilat in subtotal nephrectomy-salt hypertension: role of calcitonin gene-related peptide.
MedLine Citation:
PMID:  11566959     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 approximately 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.
Authors:
S C Supowit; H Zhao; D H Wang; D J DiPette
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  38     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-09-21     Completed Date:  2001-10-25     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  697-700     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / pharmacology*,  therapeutic use
Blood Pressure / drug effects
Blotting, Northern
Calcitonin Gene-Related Peptide / genetics,  metabolism,  pharmacology,  physiology
Cardiomegaly / drug therapy,  physiopathology
Hypertension / drug therapy*,  etiology,  physiopathology
Male
Nephrectomy
Peptide Fragments / pharmacology
Pyridines / pharmacology*,  therapeutic use
RNA, Messenger / drug effects,  genetics,  metabolism
Rats
Rats, Sprague-Dawley
Sodium Chloride, Dietary / adverse effects
Thiazepines / pharmacology*,  therapeutic use
Grant Support
ID/Acronym/Agency:
HL-44277/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Peptide Fragments; 0/Pyridines; 0/RNA, Messenger; 0/Sodium Chloride, Dietary; 0/Thiazepines; 119911-68-1/calcitonin gene-related peptide (8-37); 36NLI90E7T/omapatrilat; 83652-28-2/Calcitonin Gene-Related Peptide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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