Factors involved in delaying the rise in peripheral resistance in developing heart failure

The development of heart failure (HF) on peripheral vascular control was studied in 10 conscious dogs with measurements of cardiac output (CO) and left ventricular (LV), arterial, and right atrial pressures. At 3 wk after pacing-induced HF, CO was not decreased from 2.5 +/- 0.2 l/min, whereas LV dP/dt fell (from 2,858 +/- 71 to 1,409 +/- 69 mmHg/s) and LV end-diastolic pressure increased (from 4.8 +/- 0.4 to 27.3 +/- 1.1 mmHg) (P < 0.05). At 4-7 wk after pacing, CO was significantly decreased (to 1.6 +/- 0.1 l/min; P < 0.05), but total peripheral resistance (TPR) did not rise, despite increases in plasma norepinephrine and renin activity (P < 0.05). In the presence of ganglionic blockade, TPR was still not increased in HF. In vitro studies in isolated femoral artery segments demonstrated reduced intrinsic tone (0.028 +/- 0.007 g/mg; P < 0.05) as compared with vessels from sham-operated controls (0.124 +/- 0.023 g/mg), whereas the intracellular calcium level was not altered in HF. Thus, during the development of HF, severe contractile dysfunction precedes the fall in CO, which, in turn, precedes the rise in TPR. The delayed rise in TPR appears to involve a reduction in intrinsic peripheral vascular tone, despite neurohumoral activation.