Reduced Basal NO-mediated Dilation and Decreased Endothelial NO-synthase Expression in Coronary Vessels of Spontaneously Hypertensive Rats

Raloxifene Improves Endothelial Dysfunction in Hypertension by Reduced Oxidative Stress and Enhanced Nitric Oxide Production

“…It is known that increased oxidative stress, mediated by decreased bioavailability of NO because of enhanced superoxide production and reduced eNOS activity, is involved in the pathology of SHR. 44,45 Our findings indicate that compared with healthy age-matched Wistar rats, SHR used in our study display a higher membrane rac1 GTPase expression and activity and increased nox1 expression, leading to an increased activation of the NAD(P)H oxidase, and a lower eNOS expression and activity in aortic homogenates. This higher level of activation in SHR is normalized by treatment with raloxifene, because expression and activity of rac1 GTPase and vascular superoxide production are profoundly decreased, expression and activity of eNOS are enhanced, and, finally, endothelial function is significantly improved after treatment with SERMs.…”

Nitric oxide and coronary vascular endothelium adaptations in hypertension

“…Vascular resistance is dependent on position in the vascular network with approximately 75% of the resistance lying in the arteries between 75-200 µm in diameter, 2,5,7 and resistance also varies depending on the location of the vasculature within the depth of the myocardium. 2,5,8 Several human [9][10][11][12] and experimental animal [13][14][15][16][17][18][19][20][21][22] studies indicate that coronary vascular resistance is increased, and coronary flow reserve is decreased with hypertension. The pathophysiology of hypertension is undoubtedly heterogeneous and a variety of animal models have been developed to investigate essential hypertension.…”

“…The spontaneously hypertensive rat (SHR) model has been particularly useful since several defining characteristics of the SHR are similar to those observed in human essential hypertension including hemodynamic abnormalities, humoral and sympathetic nervous system involvement, renal abnormalities and vascular cellular adaptations. [23][24][25][26][27][28] For example, even though SHR can have similar coronary blood flow compared to their normotensive counterpart Wistar-Kyoto rats (WKY) on a ventricular mass-corrected basis, 13 SHRs have higher coronary vascular resistance (CVR) over a wide pressure range, 14,19 and higher minimal CVR (lower maximal conductance) during maximal coronary vasodilation. 13,16 Changes in coronary hemodynamics accompanying hypertension occur as a result of both structural and functional adaptations in the coronary vasculature.…”

“…29,30 A number of genetic, neurohumoral, and local factors contribute. 9,11,19,[29][30][31][32][33][34][35][36] to these adaptations which result in increases in resistance, as well as reduced flow and increased diffusion distances, all of which impair oxygen delivery and organ function. Although nitric oxide (NO) likely contributes to the structural remodeling accompanying hypertension, the focus of this review does not include description of structural adaptations, and the reader is referred to other works dealing with these topics.…”

Impaired Regulation of Renal Oxygen Consumption in Spontaneously Hypertensive Rats

“…In a model of genetic hypertension in the rat, the spontaneously hypertensive rat (SHR), abnormalities in synthesis of NO, expression of the NO-synthesizing enzymes, or both have been described both in vitro and in vivo, but with conflicting results. Thus, several studies have been performed to provide evidence of impaired vasodilation in response to acetylcholine, an effect mediated by endothelium-derived relaxing factor or NO, decreased eNOS expression, or decreased NO synthesis in SHR (5)(6)(7)(8)(9)(10)(11). These abnormalities are present as early as 5 wk of age, a period before the development of hypertension (7).…”