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

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-1) 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 endothelium-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.