Effect of insulin on renal sodium handling in hypertensive rats.

Abstract

Spontaneously hypertensive rats have reduced peripheral insulin sensitivity. To determine whether hypertensive rats demonstrate reduced response to the antinatriuretic effect of insulin, urinary sodium excretion was determined in hypertensive and normotensive rats (n=7 per group) before and during euglycemic insulin administration at two infusion rates (21 milliunits/kg load and 4 milliunits/kg/min or 85 milliunits/kg load and 8 milliunits/kg/min). Hypertensive and normotensive time controls received the vehicle for insulin administration. Mean arterial pressure was greater (/?<0.05) and inulin clearance was less (/?<0.05) in hypertensive than normotensive rats before insulin infusion. Baseline fractional sodium excretion was not different between groups. Low dose insulin infusion reduced (p<0.05) fractional sodium excretion from 0.81 ±0.43% to 0.31 ±0.07% in hypertensive rats and from 1.05±0.37% to 0.47±0.18% in normotensive rats. High dose insulin infusion reduced (/><0.05) fractional sodium excretion from 0.67±0.22% to 0.21 ±0.08% in hypertensive rats and from 0.81 ±0.15% to 0.30±0.09% in normotensive rats. Sodium excretion was unchanged in time controls. The reduction in sodium excretion was similar in both rat groups during low dose and high dose insulin infusions. Mean arterial pressure and inulin clearance were unchanged from baseline values during insulin infusion in all rat groups. Glucose requirement to maintain euglycemia was greater (p<0.05) in normotensive than hypertensive rats at both insulin infusion rates. Thus, while hypertensive rats have reduced sensitivity to the hypoglycemic effects of insulin, the antinatriuretic response to insulin is not different from that of normotensive rats. Furthermore, the presence of hypertension does not modulate the antinatriuretic activity of insulin. (Hypertension 1990;15:514-518) E levated plasma insulin levels and resistance to the hypoglycemic effect of insulin have been associated with hypertension in human and animal models of hypertension. -4 This observation • has led to speculation that insulin may play a role in the development of increased blood pressure.5 Such a hypothesis is strengthened by studies demonstrating that normotensive rats fed a fructose-enriched diet developed insulin resistance, hyperinsulinemia, and hypertension.3 Inasmuch as insulin reduces urinary sodium excretion, 6 " 8 an attractive hypothesis is that sodium-dependent hypertension develops as a result of persistent insulin antinatriuresis. However, no data are available that examine the effect of insulin on renal sodium reabsorption under conditions of elevated blood pressure. This information is fundamental for evaluation of any hypothesis implicating a role for insulin in development or maintenance of hypertension. The current study was performed to examine the effect of insulin on urinary sodium excretion in glucose-clamped, volumeexpanded spontaneously hypertensive rats (SHR). Effect of insulin on urinary sodium excretion in normotensive Wistar-Kyoto (WKY) rats was also perfo...

The Interrelationships between Fasting Serum Insulin Level, Obesity and Blood Pressure in Women: Results from a Cross-Sectional Population Study of Women in Gothenburg, Sweden.

“…Insulin increases sodium and water reabsorption in the proximal tubules of the kidney (22). Even with increased peripheral insulin resistance, as in hypertension (23) and obesity (24), the effect of insulin in the kidney seems to be preserved. Insulin also affects monoamine metabolism in the hypothalamus, resulting in increased sympathetic activity (25).…”

Link between Insulin Resistance and Hypertension: What Have We Learned from Our Ancestors?

“…Interestingly, insulin has been shown to reduce urinary sodium excretion by increased renal tubular sodium reabsorption [23]. It is unknown whether this antinatriuretic effect of insulin enhanced survival in our malnourished ancestors by promoting sodium preservation.…”

Insulin resistance and blood pressure regulation in obese and nonobese subjects. Special lecture.

“…Finally, a number of investigators have demonstrated that insulin resistance and hyperinsulinemia also are seen in spontaneously hypertensive rats. 28 " 30 In addition, insulinstimulated glucose uptake has been reported to be lower in adipocytes isolated from these animals. 29 Thus, based on this data it would appear that insulin resistance and hypertension are directly and possibly even causally related; however, data also suggest that the relation between insulin and hypertension is not so straightforward.…”