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Abstract

Responsiveness to many contractile agonists increase in deoxycorticosterone acetate (DOCA)-salt induced hypertension We tested the hypothesis that enhanced contractility of rat aorta to norepinephrine (NE) in DOCA-salt hypertension is causally related to increased expression and activity of COX-2. Thoracic aortic rings were obtained from uninephrectomized rats fed for 3 weeks on either normal (control), or 8% sodium+potassium (experimental) diets. The control and experimental groups were implanted (s.c) with placebo and DOCA (100 mg) 21-day release pellets, respectively. Tissue force of rings bathed with physiologic salt solution (PSS) (37°C;5%CO2/95%O2) were measured with FT 03 force transducers coupled to a Grass polygraph. Tail cuff pressures (mmHg) were 180 ± 5/166 ± 5 (DOCA-salt) versus 128 ± 3/116 ± 6 (Control) rats. NE (0.001-1 μM) elicited contractions of endothelium-intact and denuded aortic rings; pD2 values for intact vessels were 7.04 ± 0.05 (Control) and 8.14 ± 0.05 (DOCA). NS-398 (3 μM),a COX-2-selective blocker, reduced NE contractions in Control (24 ± 3%) and DOCA-salt (89 ± 1.8%) aortic rings. Indomethacin (10 μM), a dual COX-1/COX-2 blocker, failed to alter NE contractions in the control, but reduced the contractions of DOCA hypertensive vessels by 46 ± 5%. Piroxicam (10 μM), a COX-1-selective blocker did not alter NE contractions. Western blot analysis showed COX-2 immunoreactive bands (70 kDa) and is significantly denser on densitometric units in DOCA-salt hypertensive versus control normotensive vessels. COX-1 protein expressions were not different in control normotensive and DOCA-salt hypertensive aortic vessels. We conclude: (1) that COX-2 expression increases significantly in DOCA-salt hypertension. (2) COX-2 mediates the production of a factor(s) that enhances rat aortic contractility.

Support: Jewish Hospital Foundation, Louisville, KY; American Heart Association, Ohio Valley Affiliate.

DOCA-salt hypertension, COX-2 expression, Rat aorta
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© American Journal of Hypertension, Ltd. 2001
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