Somatostatin inhibition of fructose-induced hypertension.

Abstract

The role of insulin resistance and byperinsulinemia in the etiology of fructose-induced hypertension was studied in male Sprague-Dawley rats. Rats consumed a fructose-enriched diet (containing 66% of total calories as fructose) for 11 days and were infused continuously during the last 7 days with either a somatostatin analogue or vehicle. At the end of this period, rats receiving the somatostatin analogue had a lower plasma insulin concentration (52±4 vs. 70±6 /iunits/ml, /><0.01) and a lower blood pressure (133±2 vs. 150±2 mm Hg) than did the rats infused with the control solution. In addition, the increase in plasma triglyceride concentration in response to the fructose-enriched diet was significantly attenuated (p<0.001) in the rats infused with somatostatin. These data provide further support that the increase in blood pressure that occurs when normal rats are fed a high fructose diet is dependent on the ability of this intervention to cause insulin resistance and hyperinsulinemia. and the hyperinsulinemia appears to be associated with resistance to insulin-stimulated glucose uptake.5 ' 6 Sprague-Dawley rats become insulin resistant, hyperinsulinemic, and hypertrigryceridemic when fed a fructose-enriched diet, 7 -8 and the fact that this dietary manipulation also leads to an increase in blood pressure 8 lends further support to the possibility that insulin resistance and hyperinsulinemia may play a role in the genesis of high blood pressure. Furthermore, we have shown that exercise training of rats, which enhances insulin sensitivity 9 and reduces fructose-induced hyperinsulinemia, 10 also attenuates the increase in blood pressure seen in fructose-fed rats. 11The present experiments were initiated to further study the relation between insulin-resistance, hyperinsulinemia, and hypertension in fructosefed rats and were based on the use of somatostatin Received September 1, 1988; accepted February 14, 1989. to suppress insulin secretion by /3 cells in pancreatic islets. We reasoned that the infusion of somatostatin would suppress the hyperinsulinemia that normally results when rats are fed a fructoseenriched diet, 7 -8 -10 ' 11 and if elevated plasma insulin concentrations play a role in fructose-induced hypertension, this intervention would also ameliorate the rise in blood pressure that occurs when rats eat a high fructose diet. The results indicated that this prediction was borne out, providing further support for the view that insulin plays a role in the regulation of blood pressure in rats with fructose-induced hypertension. Materials and Methods General ProtocolMale Sprague-Dawley rats (Simonsen Laboratories, Gilroy, California), initially weighing 160-180 g, were used for all experiments. Before dietary manipulation, all rats were fed standard rat chow (Wayne Lab Blox, Allied Mills, Chicago, Illinois) containing 60% vegetable starch, 11% fat, and 29% protein and were maintained on a 12-hour light/dark (6:00 AM-6:00 PM) cycle. In addition, rats were acclimated to the procedure of blood pressure measure...

The vasodilator action of insulin. Implications for the insulin hypothesis of hypertension.

“…Somatostatin prevents both the hyperinsulinemia and the hypertension in this experimental model. 52 Somatostatin infused over 8 hours has also been reported to decrease arterial pressure (by approximately 14 mm Hg) in obese, hyperinsulinemic hypertensive humans but not in normoinsulinemic hypertensive humans. 51 These findings are intriguing but do not necessarily support the hypothesis that hyperinsulinemia causes hypertension in the presence of insulin resistance.…”

Effects of Angiotensin II Receptor Antagonists on Insulin Resistance Syndrome and Leptin in Sucrose-Fed Spontaneously Hypertensive Rats.

“…Hypertension-induced insulin resistance has been demonstrated to accompany increased skeletal muscle vascular resistance (25). Additionally, it has been reported that sucrose feeding increases norepinephrine excretion, turnover, and plasma concentration and enhances sympathetic nerve responses in rats (26,27). Thus sympathetic overactivity may be involved in the pathogenesis of this model, and may be responsible at least in part for the impairment of blood flow to skeletal muscle, which in turn would favor the development of insulin resistance (28).…”

Metabolic abnormalities of hypertension. A lesson in complexity.

“…10 These effects of fructose can be prevented by exercise training 11 or somatostatin. 12 These findings make for a body of cogent experimental evidence, although for the sake of fairness, one should mention that neither SHR nor Dahl rats have been found to be insulin resistant in vivo during euglycemic hyperinsulinemia. 13 3) In schoolchildren surveyed in Bogalusa, Louisiana, both glucose and insulin concentrations predicted higher blood pressure levels, and parental history of diabetes was associated with higher cholesterol.…”