TY - JOUR
T1 - Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats
AU - Chen, Shanwan
AU - Yuan, Christina
AU - Clough, David
AU - Schooley, James
AU - Haddy, Francis J.
AU - Pamnani, Motilal B.
N1 - Funding Information:
Received September 30, 1992. Accepted January 25, 1993. pertension in both insulin-dependent and From the Department of Physiology, Uniformed Services Univernon - insulin-dependent diabetes mellitus is not sity of the Health Sciences, Bethesda, Maryland. Tknown. In type I, insulin-dependent diabetes Dr. Pamnani is supported in part by grants from the National Heart, Lung, and Blood Institute and the Uniformed Services University of mellitus (IDDM), blood pressure tends to increase when the Health Sciences. microalbuminuria becomes apparent,1,2 suggesting that Address correspondence and reprint requests to Motilal B. Pam-even in its early stages, diabetic nephropathy may in nani, MD, PhD, Department of Physiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD some way promote hypertension. Although hyperten 20814-4799. sion is commonly associated with diabetes in humans, 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. Am J Hypertens 1993;6:397-406
PY - 1993/5
Y1 - 1993/5
N2 - 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-in- duced IDDM (25-DM), 2) normal rats with STZ-in- duced 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 di- goxin-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. Am J Hypertens 1993;6:397-406.
AB - 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-in- duced IDDM (25-DM), 2) normal rats with STZ-in- duced 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 di- goxin-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. Am J Hypertens 1993;6:397-406.
KW - Diabetes mellitus
KW - Endogenous digitalis-like substance
KW - Hypertension
KW - Reduced renal mass
KW - Streptozotocin
KW - Wistar rats
UR - http://www.scopus.com/inward/record.url?scp=84963094415&partnerID=8YFLogxK
U2 - 10.1093/ajh/6.5.397
DO - 10.1093/ajh/6.5.397
M3 - Article
C2 - 8390268
AN - SCOPUS:84963094415
SN - 0895-7061
VL - 6
SP - 376
EP - 381
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 5
ER -