Omapatrilat in subtotal nephrectomy-salt hypertension - Role of calcitoningene-related peptide

Citation
Sc. Supowit et al., Omapatrilat in subtotal nephrectomy-salt hypertension - Role of calcitoningene-related peptide, HYPERTENSIO, 38(3), 2001, pp. 697-700
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
HYPERTENSION
ISSN journal
0194-911X → ACNP
Volume
38
Issue
3
Year of publication
2001
Part
2
Supplement
S
Pages
697 - 700
Database
ISI
SICI code
0194-911X(200109)38:3<697:OISNH->2.0.ZU;2-T
Abstract
Calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide, plays a counterregulatory role in subtotal nephrectomy-salt (SN-salt)-induc ed hypertension, reflecting a stimulation of the efferent vasodilator funct ion 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) sh am-operated plus salt and omapatrilat. After I I days the mean arterial pre ssure was higher in the SN-salt group (174 +/- 10 mm Hg) versus the sham-op erated-salt (109 +/- 4 mmHg) 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 spe cific CGRP receptor antagonist produced a significant 10 2 mm Hg mean arter ial pressure increase in the untreated SN-salt hypertensive rats but was wi thout effect in the other groups. This indicates that CGRP does not contrib ute to the antiltypertensive actions of omapatrilat. In addition, CGRP mRNA and protein content in dorsal root ganglia were decreased approximate to 2 5% in the SN-salt plus omapatrilat rats. Thus, omapatrilat not only markedl y reduces the blood pressure in this model of renal failure-induced hyperte nsion but may also prevent the abnormal compensatory stimulation of the vas odilator activity of the peripheral sensory nervous system.