These results suggest that higher plasma IRI levels and/or insulin resistance are closely related to the pathogenesis of hypertension in patients with diabetes mellitus. Homa's index, fasting and sigmaIRI may be useful predictors of the subsequent development of hypertension.

To clarify the relationship between blood pressure and insulin resistance, we studied the role of glucose transporter 4 (GLUT4) in skeletal muscle and the effect of angiotensin-converting enzyme inhibitor on insulin resistance. Blood pressure and plasma glucose and plasma insulin responses to glucose loading (2 glkg, ip) were measured in spontaneously hypertensive rats (SHRs), Wistar-Kyoto rats (WKYs), and Wistar rats at 8, 12, and 20 wk of age. GLUT4 gene expression and plasma membrane protein content were also determined in the gastrocnemius muscle. SHRs and WKYs at the age of 8 wk had significantly higher plasma glucose levels than did age-matched control Wistar rats. Insulin response also tended to be higher. Glucose intolerance was also present in 12-wk-old SHRs, but normalized at the age of 20 wk. In contrast, WKYs were glucose intolerant at 12 and 20 wk. Gene expression and plasma membrane content of GLUT4 were augmented in both 8-wk-old SHRs and WKYs, indicating a compensatory increase in these variables. Effects of captopril (20-30 mg/kg/d from 8 to 20 wk) on GLUT4 were also investigated in these three strains. Captopril improved steady state plasma glucose levels in association with 1.2-to 2.5-fold higher GLUT4 gene expression and a 1.4-fold increase in skeletal muscle GLUT4 protein in SHRs and WKYs. Our results suggest that (1) not only SHRs but also WKYs may have glucose intolerance and hence insulin resistance; (2) gene expression and protein synthesis of skeletal muscle GLUT4 are probably increased compensatorily, indicating that abnormalities in GLUT4 do not have a pivotal role in the development of insulin resistance in SHRs and WKYs; and (3) captopril stimulates skeletal muscle gene expression and synthesis of GLUT4, providing further evidence of its beneficial effect on glucose metabolism. (Hypertens Res 1997; 20: 279-286)

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It is well known that diabetes mellitus is often associated with hypertension. We previously reported the unresponsiveness of renin release to volume depletion with impaired renal prostaglandin E^ synthesis in rats with streptozotocin-induced diabetes. However, we have found that BioBreeding Worcester rats, spontaneously susceptible to diabetes mellitus either before or after the onset of diabetes, showed a pronounced fourfold to ninefold increase in plasma renin activity in comparison with control Wistar rats. Furthermore, these rats developed mild hypertension as high as 134 mm Hg after the age of 90 days. The hyperreninemia responded to 1-week sodium loading or restriction; the blood pressure increased during sodium loading. Oral administration of captopril (30 mg/kg) for 1 week resulted in a large blood pressure decrease (-47.1±5.9 mm Hg, n=10) in comparison with controls (-17.0±4.7 mm Hg, n=12). Vascular response to angiotensin II was also attenuated. Plasma angiotensin II levels were 5.7-fold higher and associated with a 1.5-fold increase of plasma aldosterone concentration compared with control rats, whereas angiotensinogen-plasma concentrations were lower than in control rats. The renal renin content determined enzymatically or histochemically was more enhanced in BioBreeding Worcester rats than in control rats, but the renal renin messenger RNA levels did not differ. These results suggest that the strainspecific hyperreninemia in BioBreeding Worcester rats might be due to posttranscriptional abnormalities of renal renin synthesis. Further work is needed to elucidate the specific mechanism or mechanisms responsible. {Hypertension 1990;15:854-860)