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  • Title: Cyclooxygenase and thromboxane/prostaglandin receptor contribute to aortic endothelium-dependent dysfunction in aging female spontaneously hypertensive rats.
    Author: Graham DA, Rush JW.
    Journal: J Appl Physiol (1985); 2009 Oct; 107(4):1059-67. PubMed ID: 19696359.
    Abstract:
    Cyclooxygenase (COX)-derived vasoconstrictory prostanoids contribute to impaired endothelium-dependent vasorelaxation in aging male (m) spontaneously hypertensive rats (SHR); however, vasomotor responses in aging female (f) SHR and sex differences in aging SHR are unknown. Examining mechanisms governing dysfunction in aging fSHR will contribute to understanding sex-dependent vascular complications in advanced hypertension. Aortic endothelium-dependent relaxation dose responses (ACh) of 16- and 30-wk-old mSHR and fSHR and normotensive Wistar-Kyoto rats were examined in the absence (no drug control) and presence of COX inhibition [indomethacin (Indo)] and thromboxane/prostaglandin receptor inhibition (SQ-29548). No drug control-treated 16-wk mSHR exhibited considerable blunting of the peak relaxation response to ACh (e.g., 77 +/- 4% relaxation to 10(-5) mol/l) vs. Wistar-Kyoto controls (89 +/- 6%), and greater dysfunction occurred in 30-wk mSHR (63 +/- 2%). Interestingly, ACh relaxations of fSHR were unimpaired at 16 wk (101 +/- 2% to 10(-5) mol/l), but blunted in 30 wk (76 +/- 4%). Indo and SQ-29548 restored robust ACh vasorelaxation in all groups (e.g., 113 +/- 3 and 112 +/- 3%, respectively, in Indo- and SQ-29548-treated 30-wk fSHR). Aortic COX-1 protein expression was elevated by 75% in 30-wk vs. 16-wk fSHR, whereas group-averaged ACh-stimulated aortic PGI(2) release (assessed as 6- keto-PGF(1alpha)) was 30% greater in 30-wk vs. 16-wk fSHR (9,926 +/- 890 vs. 7,621 +/- 690 pg.ml(-1).mg dry wt(-1)), although this did not reach significance (P = 0.0758). Dramatic deterioration of endothelium-dependent vasomotor function in fSHR across this age range involves COX and thromboxane/prostaglandin receptor, supporting a mechanism of impairment similar to that which occurs in aging mSHR.
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