GLUCOCORTICOID MODULATES VASODILATOR RESPONSE OF MESENTERIC ARTERIOLES IN SPONTANEOUSLY HYPERTENSIVE RATS

We previously reported that the response of the arterioles in spontane ously hypertensive rats (SHR) to histamine is blunted compared with th at in normotensive control rats (Wistar-Kyoto rats [WKY]). The present study was designed to analyze the extent to which this blunted arteri olar response may be attributed in SHR to the concurrent elevation of circulating glucocorticoids through the use of adrenalectomy with and without dexamethasone supplementation. Mesenteric arterioles were obse rved by intravital microscopy under general anesthesia, and their lume n diameters were measured after histamine superfusion. The concentrati on-response curve with histamine was compared with that of an endothel ium-independent vasodilator, sodium nitroprusside. At the end of each experiment, papaverine was applied topically to determine the maximal diameter for each vessel, from which a measure of arteriolar tone coul d be computed. The arteriolar tone in sham-operated SHR is set at a hi gher steady-stare level than in sham-operated WKY. The concentration r equired for a 50% dilator response (EC(50)) of histamine in adrenalect omized SHR was restored to the level of WKY. Adrenalectomy did not sig nificantly affect the EC(50) of histamine in WKY. When adrenalectomize d SHR received a supplement of dexamethasone, the arteriolar response was found to show the same refractory pattern to histamine as sham-ope rated SHR. In contrast, the EC(50) of sodium nitroprusside in sham-ope rated and adrenalectomized SHR was similar to that in sham-operated WK Y. Our results indicate that the impaired dilator response to histamin e in SHR is related to an enhanced adrenal glucocorticoid secretion.