SUMMARY Possible alterations in mesenteric vascular reactivity to norepinephrine, angiotensin II, and arginine vasopressin and its relationship to prostaglandins in dexamethasone-induced hypertension in rats were investigated. The animals were treated with dexamethasone or its vehicle (sesame oil) for I day (1.8 mg/kg) and for 14 days (1.8 mg/kg/wk). The superior mesenteric artery with its branches was isolated and perfused with Tyrode's solution at a constant flow rate of 5 ml/min. Administration of norepinephrine (1-10 nmol), arginine vasopressin (0.03-0.3 nmol), or angiotensin II (0.1-1 nmol) produced vasoconstriction and increased the output of 6-keto-prostaglandin F ln and prostaglandin E 2 in a dose-related manner in mesenteric vessels. Administration of 10 nmol bradykinin or 19 nmol A23187 enhanced the output of prostaglandins without altering vascular tone. The vasoconstrictor response to arginine vasopressin, but not norepinephrine or angiotensin II, was enhanced in mesenteric vessels from rats treated with dexamethasone for 14 days but not for 1 day. In contrast, the output of basal as well as norepinephrine, arginine vasopressin, angiotensin II, bradykinin, or A23187-induced prostaglandin output was significantly reduced in mesenteric vessels from rats treated with dexamethasone for 1 or 14 days. Prostaglandin output in mesenteric arteries from rats treated with dexamethasone for 1 and 14 days was not different. These data indicate that dexamethasone treatment for longer but not for shorter periods results in a selective increase in vascular reactivity of mesenteric vessels to arginine vasopressin that is independent of prostaglandin synthesis. The increase in vascular reactivity to arginine vasopressin during long-term dexamethasone treatment may contribute to the development or maintenance, or both, of glucocorticoid-induced hypertension. 198S) KKV WORDS • dexamethasone-induced hypertension • vascular responsiveness 6-keto-prostaglandin F, ( , • prostaglandin E 2 • perfused mesenteric artery G LUCOCORT1COID treatment over a pro-' longed period in some animal species or glucocorticoid excess in patients with Cushing's syndrome results in arterial hypertension.1 " 1 The demonstration by some investigators that glucocorticoid excess enhances the pressor response and vascular reactivity to norepinephrine (NE) in animals and humans suggests that this effect contributes to the pathogenesis of glucocorticoid-induced hypertension.5 "" The increase in vascular reactivity to NE caused by long-term treatment with glucocorticoids appears to be unrelated to their action to inhibit extraneuronal uptake or meta-

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The effects of secretin, cholecystokinin, dopamine, histamine and acetylcholine on the secretion of pancreatic juice were investigated in the monkey and the dog. In the resting state, bicarbonate concentration and the volume of pancreatic juice in the monkey were greater than those in the dog. However, the protein concentration of pancreatic juice in the monkey was less than that in the dog. Intravenous administration of secretin, cholecystokinin, histamine and acetylcholine caused a dose dependent increase in pancreatic secretion in both species. The responses in the monkey were greater than those in the dog. Dopamine caused pancreatic secretion only in the dog. The increase in bicarbonate concentrations of pancreatic juice induced by secretin and histamine in the monkey were greater than that in the dog. Increase in protein concentrations of the juice induced by cholecystokinin and acetylcholine in the monkey were less than that in the dog. However, pancreatic juice pH in both species was the same and was not affected by the secretagogues in the resting state or during the stimulation by secretogogues. From these results, it is concluded that there is a species difference in the secretory actions of the secretagogues in the monkey and the dog.

Our previous finding that dexamethasone-induced hypertension in rats is associated with enhanced reactivity of mesenteric arteries to arginine vasopressin but not to angiotensin II (Ang II) or norepinephrine has led us to postulate that vasopressin contributes to the development or maintenance of glucocorticoid-induced hypertension. To test this view, we investigated the effects of vasopressin, Ang II, norepinephrine, and the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP on mean arterial blood pressure and heart rate with and without ganglionic blockade with hexamethonium and angiotensin I (Ang I) converting enzyme inhibition with MK 421 in pentobarbital-anesthetized rats made hypertensive by treatment with dexamethasone (1.8 mg/kg/wk for 14 days). Administration of vasopressin, Ang II, or norepinephrine (0.003-3 microgram i.v.) produced a dose-related increase in arterial blood pressure. The pressor response to vasopressin, but not to Ang II or norepinephrine, was greater in dexamethasone-treated than in vehicle-treated animals, and this difference became more pronounced in rats that received hexamethonium and MK 421. Administration of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced arterial pressure in dexamethasone-treated but not in vehicle-treated animals. Hexamethonium and MK 421 reduced arterial blood pressure in dexamethasone-treated as well as in vehicle-treated rats; however, arterial blood pressure remained higher in the former. Administration of the vasopressin V1 receptor antagonist produced a greater reduction in arterial blood pressure in dexamethasone-treated than in vehicle-treated rats. These data suggest that vasopressin contributes to glucocorticoid-induced hypertension, which is probably due to enhanced vascular reactivity to the peptide.

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