Effect of Insulin on Norepinephrine Overflow at Peripheral Sympathetic Nerve Endings in Young Spontaneously Hypertensive Rats

To determine how the effect of insulin is related to the development of salt-induced hypertension, and whether a hyporesponse to insulin exists in the peripheral sympathetic nerves of a hypertensive model rat, we measured norepinephrine overflow from the periarterial nerve of isolated mesenteric arteries exposed to insulin in spontaneously hypertensive rats (SHR) as well as Wistar-Kyoto rats (WKY) fed diets that were high and low in salt. Salt loading (diet containing 8% salt for 4 weeks) accelerated the development of hypertension in young, spontaneously hypertensive rats (SHR) (157 ± 5 mm Hg υ 198 ± 4 mm Hg, P< .01) but did not affect the blood pressure of Wistar-Kyoto rats (WKY) (102 ± 7 mm Hg υ 104 ± 6 mm Hg, P = NS). Basal norepinephrine overflow did not differ in the SHR and WKY rats, but the overflow of norepinephrine after periarterial electrical stimulation (8 Hz 1 min.) was significantly greater in SHR (0.806 ± 0.079 ng/g) than in WKY (0.723 ± 0.022 ng/g P< .01). Although insulin reduced the norepinephrine overflow by periarterial nerve stimulation in both WKY and SHR, the decrease with insulin was significantly greater in the SHR than in WKY (−18.4% ± 4.0% υ −32.0% ± 4.6%, P< .05). The inhibitory effect of insulin on norepinephrine overflow was reduced by salt loading in SHR (−8.8% ± 4.0%, P< .05), but not in WKY (−32.5% ± 4.7%, P = NS). Cocaine and ouabain completely blocked the effect of insulin in all four groups. In contrast to insulin, direct stimulation of Na+-K+ ATPase with a high-potassium buffer (12 mmol/L) reduced NE overflow to the same extent among the four groups. These findings show that SHR have a blunted response to the suppression by insulin of norepinephrine overflow. Salt loading reduced the insulin response at peripheral sympathetic nerves of young SHR, but did not affect that of age-matched WKY. Thus, hyporeactivity to insulin may play a role in the development of salt-induced hypertension in young SHR, possibly through a reduced suppression of norepinephrine overflow from sympathetic nerve endings. Am J Hypertens 1996;9:1119–1125