EFFECTS OF GENETIC HYPERINSULINEMIA 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 th e obese Zucker rat is related to changes in vascular reactivity. Systo lic blood pressure (SEP) in conscious Zucker rats was significantly gr eater 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 (E C(50) 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 presser response to PE and depressor response to acetylcholine (ACh) and sodium nitroprusside (SNP). In the isolated aorta, from obese animals, insulin attenuated the contractile respons e to PE but markedly enhanced the vasoconstrictor potency of 5-HT. It had no significant effect on presser or depressor responses in the per fused mesenteric bed. The data suggest that increased reactivity of ce ntral arteries to spasmogenic agents may be involved in the developmen t of systolic hypertension in the hyperinsulinaemic Zucker rat.