Effects of genetic hyperinsulinaemia on vascular reactivity, blood pressure, and renal structure in the Zucker rat.

The association between insulin resistance, obesity, and hypertension is well recognised. We examined the hypothesis that hypertension in the obese Zucker rat is related to changes in vascular reactivity. Systolic blood pressure (SBP) in conscious Zucker rats was significantly greater in obese as compared with lean animals (157 +/- 9 and 117 +/- 8 mm Hg). Obese animals also had marked proteinuria and reduced urinary creatinine excretion in 24 h as compared with their lean counterparts. The reactivity of isolated aorta to phenylephrine (PE) and 5-hydroxy-tryptamine (5-HT) was modestly (twofold) increased in obese animals (EC50 13.8 nM as compared with 29.4 nM in lean animals and 0.19 nM as compared with 0.46 nM in lean animals, respectively). In the perfused mesenteric vascular bed, basal perfusion pressure was the same in both phenotypes, as was the pressor response to PE and depressor response to acetylcholine (ACh) and sodium nitroprusside (SNP). In the isolated aorta, from obese animals, insulin attenuated the contractile response to PE but markedly enhanced the vasoconstrictor potency of 5-HT. It had no significant effect on pressor or depressor responses in the perfused mesenteric bed. The data suggest that increased reactivity of central arteries to spasmogenic agents may be involved in the development of systolic hypertension in the hyperinsulinaemic Zucker rat.