Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats.
We have previously reported that chronic hypertension develops consistently in Wistar rats with a 25% reduction in renal mass (RRM) following the induction of insulin dependent diabetes mellitus (IDDM) with streptozotocin (STZ, 65 mg/kg body weight, intravenously). In this study, we examined the role of the endogenous digitalis-like substance in the development of hypertension. Four groups of rats were studied: 1) 25% RRM rats with STZ-induced IDDM (25-DM), 2) normal rats with STZ-induced IDDM (2K-DM), 3) 25% RRM rats with vehicle treatment (25-V), and 4) normal rats with vehicle treatment (2K-V). In 25-DM rats, blood pressure progressively increased during the 3 weeks after STZ treatment and was associated with microalbuminuria, low plasma renin activity, and extracellular volume expansion. In contrast, the 2K-DM, 25-V, and 2K-V rats remained normotensive. Furthermore, the plasma and urine levels of digoxin-like immunoreactive factor (DIF), determined by digoxin radioimmunoassay (Baxter), were significantly higher in hypertensive 25-DM rats than in their controls. The same was the case for plasma digitalis-like substance (DLS), determined by exposing canine Na+,K(+)-ATPase to plasma fractions and observing the percent inhibition. Increased DIF and DLS in hypertensive 25-DM rats was associated with a significant decrease in Na+,K(+)-ATPase activity of microsomes prepared from the left and right ventricles, when compared with microsomes from normotensive 2K-DM animals. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The DIF and DLS correlated significantly with each other and with myocardial Na+,K(+)-ATPase activity and mean blood pressure. These results suggest that increased endogenous digitalis-like substance, which inhibits cardiovascular muscle cell Na(+)-K(+)-pump activity, may be involved in the mechanism of hypertension associated with IDDM in 25% RRM rats.
Chen
S
S
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Yuan
C
C
Clough
D
D
Schooley
J
J
Haddy
F J
FJ
Pamnani
M B
MB
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D004070:Digitalis; D006973:Hypertension / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009392:Nephrectomy; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014556:Urine / Q000737:chemistry
D000254:Sodium-Potassium-Exchanging ATPase