Effect of digibind (DIG) on cardiovascular hemodynamics in rats with insulin dependent diabetes mellitus (IDDM) hypertension (HT)

• Published in: The FASEB journal 2007, Vol.21 (6), p.A898-A898
• Main Authors: Pamnani, Motilal B., Schooley, James F., Bryant, Howard J.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.A898-c

We have reported that IDDM HT develops consistently in rats with 25% reduction in renal mass (25%RRM) and the injection of streptozotocin (STZ). In this model, we found that, as in other types of low renin (LR), volume expanded (VE) HT in animals and humans, increased endogenous Na+‐K+ pump inhibitor (SPI), a digitalis‐like substance. Increase in SPI by inhibiting cardiovascular muscle (CVM) cells Na+‐K+pump (NKP) activity causes increased vascular resistance and cardiac contractility (dP/dt) resulting in the development of HT. The glycemic control, and altered diet, after HT was fully established in IDDM rats, failed to reverse the HT. The main endogenous HT agent in this model seems to be the SPI as we and others have reported in LR VE HT. Therfore, we have examined the effect of acutely administered DIG on the hemodynamics of IDDM‐HT rats. DIG competitively displaces SPI from its binding site on Na+, K+‐ATPase and therefore restimulates NKP and normalizes BP. Normal rats underwent 25% RRM under anesthesia. After one week, rats received a single injection of STZ, 65 mg/kg, bw. All RRM‐STZ rats developed IDDM‐HT. After 5 weeks of IDDM‐HT, the rats were divided into experimental (E) and control (C) groups. Under anesthesia, BP, dP/dt and urine excretion were measured. At the end of the C period, the E rats received an iv infusion of DIG 30 mg/kg, bw over a 30 min period. During infusion and 60 min. post infusion, BP and dP/dt were monitored and urine collected every 10 min. The C rats underwent same procedure except, they received iv saline instead of DIG. Our preliminary results show that infusion of DIG, produced no significant effect on any of the parameters studied.