Study of mechanisms of glucocorticoid hypertension in rats: endothelial related changes and their amelioration by dietary fish oils

Abstract

1 To investigate possible mechanisms of increased systolic blood pressure after 1 weeks treatment with dexamethasone and its amelioration by fish oil feeding, we have examined the reactivity of aortic rings and perfused mesenteric resistance vessels. 2 Thirty six Sprague-Dawley rats were initially divided into two groups and fed a semisynthetic diet containing either (10% by weight) hydrogenated coconut oil and safflower oil mixture (HCO/S) (24 rats) or fish oil (12 rats) for 5 weeks. From the end of the fourth week, dexamethasone (1.25 mg ml-') in drinking water, was given to half the rats on hydrogenated coconut oil (HCO/S + Dex) and to the fish oil-fed group (fish oil + Dex). 3 One week of dexamethasone treatment raised systolic blood pressure in the HCO/S + Dex rats but not in the fish oil + Dex group. 4 Endothelium-dependent relaxation to acetylcholine (ACh) was decreased in aortic rings taken from HCO/S + Dex rats compared to rats on HCO/S alone. Relaxant responses to ACh of aortic rings from rats given fish oil + Dex were intermediate between the three groups. Aortic endothielium-independent responses to sodium nitroprusside (SNP) were unchanged between the groups, while aortic contractile responses to noradrenaline were similar in all the groups. 5 In the perfused mesenteric resistance artery, sensitivity to noradrenaline was decreased in rats given fish oil and dexamethasone compared to the other two groups. There were no differences in resistance vessel relaxation to ACh or SNP between groups. 6 Serum corticosterone levels, used as a marker of dexamethasone absorption, were substantially suppressed in dexamethasone-treated rats but levels were higher in rats on fish oil than on HCO/S diets. 7 We suggest that the glucocorticoid-induced rise in systolic blood pressure may be due in part to decreased aortic compliance as a consequence of impaired endothelium-dependent relaxation and perhaps reduced nitric oxide synthesis. Fish oil feeding may ameliorate this rise in blood pressure through (i) changes in dexamethasone absorption, (ii) decrease in reactivity to noradrenaline of perfused mesenteric resistance arteries, (iii) an increase in endothelium-dependent relaxation to ACh or a combination of these three factors.

Omega‐3 Fatty Acids and Hypertension in Humans

“…The favourable effects of DHA on vasoreactivity 10 are most likely attributable to direct and indirect effects of DHA on the arterial wall and may include DHA incorporation into endothelial membranes increasing membrane fluidity, calcium influx and endogenous synthesis and release of NO. Docosahexaenoic acid could also have direct effects on receptor‐stimulated NO release, enhanced release of vasodilator prostanoids and/or endothelial‐derived hyperpolarizing factor, consistent with experimental evidence 59 . The enhanced response to sodium nitroprusside may relate to increased biotransformation to NO or increased reactivity of smooth muscle cells to vasorelaxation as a result of decreased calcium influx 60 .…”

Decrease in the Concentrations of Transforming Growth Factor-beta1 in the Sera of Patients with Kawasaki Disease

“…The in vivo relevance of this effect at the relatively .low maintenance doses employed in our patients may be marginal (20). With regard to corticosteroids, Yin et al (21 ) have demonstrated that ACh-induced endothelium-dependent vasodilation is impaired in rats treated with dexamethasone, and Altura (22) has also found impaired vasodilator responses to bradykinin in rats treated with glucocorticoids. In addition, eNOS activity is not affected by glucocorticoids (23,24) and expression of iNOS can be prevented by steroids (24).…”

Anti‐oxidant Effects of Atorvastatin in Dexamethasone‐induced Hypertension in the Rat

“…Statins have been reported to upregulate eNOS expression, reduce endothelin‐1 expression, downregulate angiotensin II AT 1 receptor expression and inhibit NAD(P)H oxidase activity 8,9 . Inhibition of NO synthesis, thereby inhibiting the vasodilator action of NO, has been suggested as one of the mechanisms responsible for the induction of hypertension by Dex in rats 10 . Atorvastatin (Ato) normalized aortic eNOS activity and systolic blood pressure (SBP) and concomitantly reduced oxidant stress in Dahl‐salt rats 11 .…”