Abstract-The study was conducted to examine the effects of the angiotensin subtype 1 and 2 receptor antagonists (losartan and PD123319, respectively) on blood pressure (BP) and renal excretory function in chronic hyperinsulinemia-induced hypertension in rats. Hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per minute) via osmotic minipump for 6 weeks. Losartan or PD123319 was coinfused either at the beginning or after 4 weeks of insulin infusion. The results showed that insulin infusion significantly increased the plasma insulin concentration from 259.0Ϯ22.2 to 646.5Ϯ33.0 and 713.9Ϯ26.5 pmol/L (PϽ0.05) by the end of the fourth and sixth weeks, respectively, after insulin infusion. There were no significant changes in plasma glucose and triglyceride concentrations. Systolic BP increased from 139Ϯ3 to 156Ϯ1 and 157Ϯ2 mm Hg (PϽ0.05) at the corresponding time points. Combined losartan (3.5 g/kg per minute) and insulin infusion prevented the rise in BP and improved insulin resistance. When hypertension had been established after 4 weeks of insulin infusion, superimposed infusion of losartan on insulin reversed the elevated BP to control levels within 1 week. In contrast, administration of PD123319 (0.5 and 10 g/kg per minute) failed to alter insulin-induced hypertension. Combined PD123319 with losartan did not alter the losartan-induced hypotensive effect in insulin-infused rats. There were no significant differences in water intake, urine flow, body weight gain, and sodium gain before and after antagonist administration among groups. These results indicate that angiotensin type 1 receptors play a determinant role in the pathogenesis of insulin-induced hypertension in rats. (Hypertension. 1998;32:235-242.)Key Words: hyperinsulinemia Ⅲ insulin resistance Ⅲ losartan Ⅲ PD123319 Ⅲ angiotensin receptor antagonist N umerous clinical and epidemiological studies have demonstrated that essential hypertension is correlated with insulin resistance and hyperinsulinemia.1-3 The close association between hypertension and insulin resistance-hyperinsulinemia has been noted to occur in some genetically hypertensive rat models, such as spontaneously hypertensive rats, 4,5 Milan hypertensive rats, 6 and Dahl salt-sensitive rats. 7Rodents fed sucrose-, fructose-, or glucose-enriched diets can develop hypertension that is also related to insulin resistance and hyperinsulinemia. 8 -10 Moreover, exogenous insulin or fructose-feeding can accelerate and aggravate the development of hypertension in spontaneously hypertensive and Dahl salt-sensitive rats.11-14 These observations strongly suggest an etiologic link between insulin resistance-hyperinsulinemia and hypertension. This notion is further supported by the direct evidence that euglycemic hyperinsulinemia achieved by long-term insulin administration produces hypertension in the rat. [15][16][17] However, the underlying mechanism responsible for the coupling of hyperinsulinemia-insulin resistance with the pathogenesis of hypertension is not fully understood, although hyper...

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These data suggest that testosterone can promote and estrogen may inhibit calcium oxalate stone formation in EG-treated rats.

Abstract-Experiments were performed to evaluate the role of the renal nerves in hyperinsulinemia-induced hypertension.Male Sprague-Dawley rats were made hyperinsulinemic by insulin infusion via osmotic minipumps implanted subcutaneously (3.0 mU/kg per minute for 6 weeks). Rats with vehicle infusion served as controls. Bilateral renal denervation was performed either at the beginning of or 4 weeks after insulin infusion. The systolic blood pressure was measured by the tail-cuff method twice a week. Food and water intake and urine flow were measured daily. The results showed that sustained insulin infusion significantly increased plasma insulin concentrations from 277.7Ϯ25.8 pmol/L to 609.9Ϯ22.2 and 696.7Ϯ23.0 pmol/L by the end of weeks 4 and 6, respectively (PϽ0.05). Systolic blood pressure was significantly increased from 135Ϯ3 to 157Ϯ3 and 159Ϯ2 mm Hg (PϽ0.05) at the corresponding time points. There was a significant increase in the plasma norepinephrine concentration after insulin infusion, whereas no significant changes in plasma triglyceride and glucose concentrations, water intake, urine flow, sodium excretion, sodium gain, and body weight gain were observed. Bilateral renal denervation depleted renal norepinephrine stores and prevented the development of hyperinsulinemia-induced hypertension. After hyperinsulinemia-induced hypertension had been fully established (from 134Ϯ2 to 157Ϯ2 mm Hg), bilateral renal denervation reversed the elevated systolic blood pressure to normotensive levels within 2 weeks. Transient denervated diuresis and natriuresis were observed. These results indicate that chronic hyperinsulinemia-induced hypertension requires the presence of intact renal nerves in rats.(Hypertension. 1998;32:249-254.)Key Words: hyperinsulinemia Ⅲ insulin resistance Ⅲ renal nerve Ⅲ renal denervation Ⅲ denervated natriuresis N umerous studies have provided strong inferential evidence that positively associates hypertension with insulin resistance and hyperinsulinemia in humans and some genetically hypertensive rats.1-6 Sustained high carbohydrate feeding in rats results in hypertension that is also correlated with insulin resistance and hyperinsulinemia.7-9 Moreover, we and others have demonstrated that long-term insulin administration causes hypertension in rats.10 -13 The hyperinsulinemia-induced rise of blood pressure is reversible with termination of insulin infusion, thus denoting a specific effect of hyperinsulinemia. 10 These observations provide direct support for an important role for hyperinsulinemia or a hyperinsulinemia-associated mechanism in causing hypertension. However, the precise mechanism coupling hyperinsulinemia to the development of hypertension is not yet clear. Some short-term studies showed that insulin could increase the renal reabsorption of sodium and reduce sodium excretion in animals and humans.14,15 Also, acute or chronic elevation in plasma insulin level stimulates the sympathetic nervous system and increases plasma catecholamines. 16 -18 It follows that hyperinsulinemia may ...