ETAreceptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats
| Autor: | Graham H. Allcock, David M. Pollock, Richard C. Venema |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Endothelin Receptor Antagonists
Male medicine.medical_specialty Kidney Cortex Pyrrolidines Time Factors Transcription Genetic Physiology Urinary system Renal function Blood Pressure Kidney Nephrectomy Rats Sprague-Dawley Physiology (medical) Internal medicine medicine Animals RNA Messenger Desoxycorticosterone Kidney Medulla Endothelin-1 business.industry Sodium Dietary Stereoisomerism Water-Electrolyte Balance Receptor Endothelin A Endothelin 1 Rats Blockade Endocrinology Blood pressure medicine.anatomical_structure Creatinine Atrasentan Hypertension medicine.symptom Endothelin receptor business Vasoconstriction Glomerular Filtration Rate |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 275:R245-R252 |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | Endothelin (ET)-1 has potent renal and systemic vasoconstrictor properties, and thus we investigated whether ET-1 plays a role in increasing blood pressure and decreasing renal function in DOCA-salt hypertension. After a right nephrectomy, rats had DOCA or placebo pellets implanted subcutaneously and were given saline or tap water to drink, respectively. Additional groups of rats were given the ETAreceptor antagonist A-127722 in their water. Rats were maintained in metabolic cages for monitoring excretory function and food and water intake. Three weeks after surgery, mean arterial pressure (MAP) was recorded in the conscious rats via a carotid artery catheter. As expected, DOCA-salt rats had significantly higher MAP compared with uninephrectomized controls (197 ± 6 vs. 133 ± 3 mmHg). Creatinine clearance, used as an estimate of glomerular filtration rate, was significantly reduced in DOCA-salt rats (2.9 ± 0.4 vs. 6.8 ± 0.3 dl ⋅ day−1⋅ 100 g−1body wt in controls). ETAreceptor blockade with A-127722 significantly reduced MAP (156 ± 8 mmHg) but had no effect on creatinine clearance of DOCA-salt-treated rats (2.8 ± 0.3 dl ⋅ day−1⋅ 100 g−1body wt). Plasma ET-1 levels were significantly raised after DOCA-salt treatment (1.4 ± 0.5 pg/ml vs. 0.4 ± 0.1 pg/ml in controls). A-127722 treatment increased circulating ET-1 levels in both placebo (2.3 ± 0.5 pg/ml) and DOCA-salt (5.6 ± 0.7 pg/ml) rats. However, ET-1 mRNA expression in renal cortical and medullary tissue was not affected by either A-127722 or DOCA-salt treatments. Thus ETAreceptors appear to play a role in the maintenance and development of DOCA-salt hypertension but not in the accompanying reduction of renal function. |
| Databáze: | OpenAIRE |
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