ET(A) receptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats

Graham H. Allcock, Richard C Venema, David M. Pollock

Research output: Contribution to journalArticle

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Abstract

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 ET(A) receptor 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-1 body wt in controls). ET(A) receptor 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-1 body 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 ET(A) receptors appear to play a role in the maintenance and development of DOCA-salt hypertension but not in the accompanying reduction of renal function.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume275
Issue number1 44-1
StatePublished - Jul 1 1998

Fingerprint

Desoxycorticosterone Acetate
Endothelin A Receptors
Renal Hypertension
Salts
Endothelin-1
Kidney
Arterial Pressure
Creatinine
Placebos
Hypertension
Water
Vasoconstrictor Agents
Nephrectomy
Glomerular Filtration Rate
Carotid Arteries
Drinking
Therapeutics
Catheters
Eating
Maintenance

Keywords

  • Deoxycorticosterone acetate
  • Endothelin
  • Endothelin antagonist
  • Endothelin receptor

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

ET(A) receptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats. / Allcock, Graham H.; Venema, Richard C; Pollock, David M.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 275, No. 1 44-1, 01.07.1998.

Research output: Contribution to journalArticle

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abstract = "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 ET(A) receptor 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-1 body wt in controls). ET(A) receptor 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-1 body 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 ET(A) receptors appear to play a role in the maintenance and development of DOCA-salt hypertension but not in the accompanying reduction of renal function.",
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N2 - 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 ET(A) receptor 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-1 body wt in controls). ET(A) receptor 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-1 body 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 ET(A) receptors appear to play a role in the maintenance and development of DOCA-salt hypertension but not in the accompanying reduction of renal function.

AB - 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 ET(A) receptor 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-1 body wt in controls). ET(A) receptor 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-1 body 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 ET(A) receptors appear to play a role in the maintenance and development of DOCA-salt hypertension but not in the accompanying reduction of renal function.

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