Omapatrilat in Subtotal Nephrectomy-Salt Hypertension
| Autor: | Huawei Zhao, Donna H. Wang, Donald J. DiPette, Scott C. Supowit |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Mean arterial pressure medicine.medical_specialty Pyridines Thiazepines Calcitonin Gene-Related Peptide Blood Pressure Cardiomegaly Vasodilation Calcitonin gene-related peptide Nephrectomy Rats Sprague-Dawley Internal medicine Internal Medicine Animals Medicine RNA Messenger Sodium Chloride Dietary Antihypertensive Agents business.industry Blotting Northern Peptide Fragments Rats medicine.anatomical_structure Endocrinology Blood pressure Calcitonin Hypertension ACE inhibitor Omapatrilat business medicine.drug Sensory nerve |
| Zdroj: | Hypertension. 38:697-700 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hy09t1.095759 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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