Reduction of NO- and EDHF-Mediated Vasodilatation in Hypertension: Role of Asymmetric Dimethylarginine

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase (NOS), and endothelial dysfunction is related to the elevation of ADMA level in hypertension. Besides the NO-mediated pathway, the endothelium-derived hyperpolarizing factor (EDHF)-mediated pathway is involved in endothelial dysfunction. The aims of the present study were to evaluate the changes of endothelium-dependent dilatation of arteries in hypertension and the role of ADMA in NO- and EDHF-mediated vasodilatation. The great omental arteries were isolated from essential hypertensive and normotensive patients, and mesenteric arteries were isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. NO-, EDHF-, and prostaglandin (PGI(2))-mediated endothelium-dependent vasodilatation were measured, and plasma concentrations of ADMA were determined in rats. Cultured endothelial cells were treated with ADMA (1-10 microM) for 48 h, and the mRNA and protein level of small-conductance Ca(2+)-activated K(+) channel 3 (SK3), which has been thought to be a key mediator of EDHF, was determined. Both NO- and EDHF-mediated endothelium-dependent responses were decreased in the great omental arteries of hypertensive patients and mesenteric arteries of SHR. Plasma levels of ADMA were significantly increased in SHR. In cultured endothelial cells, the expressions of SK3 mRNA and protein were concentration-dependently down-regulated in the presence of ADMA. The present study suggests that the inhibitory effect of ADMA on endothelial function not only involves NO-mediated endothelium-dependent vasodilatation but also the EDHF-mediated pathways in hypertensive animals and humans, and that ADMA can down-regulate the expression of SK3 channels in endothelial cells.

Plasma-Mediated Vascular Dysfunction in the Reduced Uterine Perfusion Pressure Model of Preeclampsia

“…A diminished or absent NO-mediated vasodilatory response has previously been demonstrated in vessels from women with PE. 8 Moreover, studies have also detected a lack of NOmediated vasodilatation in conduit vessels from RUPP rats, 12,16 however the present study is the first to demonstrate this in resistance vessels treated with RUPP plasma. The remaining relaxant response in RUPP plasma-treated vessels was significantly attenuated after both cyclooxygenase inhibition and K ϩ channel blockade indicating vasorelaxant roles for both PGI 2 and EDHF, respectively.…”

“…2 Impaired endothelium-dependent responses have been reported in systemic vessels isolated from women with PE. 3,4 Moreover, numerous studies have demonstrated disparities in terms of the relative contributions of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (PGI 2 ) to vasodilatation in both physiological [5][6][7][8] and pathophysiological pregnancies. 3,6,9 In addition, the vascular dysfunction associated with PE has been shown to be induced by one or more circulating mediators as impaired relaxation was detected in resistance vessels exposed to plasma from women with PE.…”

Association of Endodontic Infection with Detection of an Initial Lesion to the Cardiovascular System

“…Major agreement has been reached as to the prominent role played by ADMA in the pathogenesis and progression of CVD, specifically atherosclerosis. An independent relationship between ADMA and the incidence of major clinical conditions such as hypertension (38), heart failure (39), coronary heart disease (40) and diabetes (41), and CV death (42) has been demonstrated. Serum ADMA levels allow a more detailed risk analysis to be performed when compared with the traditional CV risk markers.…”

Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats

“…Interestingly, ADMA levels have been shown to be higher in male SHR compared with male WKY rats in plasma and isolated hearts, indicating an increase with hypertension (26,27) higher in men than in women (21). It is plausible, therefore, to speculate that sex differences in ADMA and DDAH may contribute to sex differences in cGMP levels in the kidney.…”