Decreased cardiac output at the onset of diabetes: renal mechanisms and peripheral vasoconstriction

Recently we reported that hindquarter blood flow, measured 24 h/day, decrea sed progressively over the first 6 days of type 1 diabetes in rats. That re sponse, coupled with the tendency of mean arterial pressure to increase, su ggested a vasoconstrictor response. The purpose of this study was to measur e the changes in cardiac output together with the renal hemodynamic and exc retory responses to allow integrative determination of whether vasoconstric tion likely accompanies the onset of type 1 diabetes. Rats were instrumente d with a Transonic flow probe on the ascending aorta and with artery and ve in catheters, and cardiac output and mean arterial pressure were measured c ontinuously, 24 h/day, throughout the study. The induction of diabetes, by withdrawing intravenous insulin-replacement therapy in streptozotocin-treat ed rats, caused a progressive decrease in cardiac output that was 85 +/- 5% of control levels by day 7. This was associated with significant increases in glomerular filtration rate, renal blood flow, and microalbuminuria as w ell as urinary fluid and sodium losses, with a negative cumulative sodium b alance averaging 15.7 +/- 1.6 meg by day 7. Restoring insulin-replacement t herapy reversed the renal excretory responses but did not correct the negat ive sodium balance, yet cardiac output returned rapidly to control values. Increasing sodium intake during the diabetic and recovery periods also did not significantly affect the cardiac output response during any period. The se results indicate that cardiac output decreases significantly at the onse t of type 1 diabetes without glycemic control, and although volume loss may contribute to this response, there also is a component that is not volume or sodium dependent. We suggest this may be due to vasoconstriction, but to what extent local blood flow autoregulation or active vasoconstriction may have mediated that response is not known.