Bioassay by cross-perfusion for circulating inotropic factor in hypertension

To study inotropic effects of blood from one-kidney, one-clip (1K,1C) rats with early (less than 7 days) or chronic (greater than 4 wk) benign hypertension, we assessed arteriolar resistance and norepinephrine (NE) responses in vascularly isolated, innervated assay hindlimb vascular beds of alpha-chloralose-anesthetized, normal male recipient rats. Hindlimbs were cross-perfused (2 ml/min) with blood from anesthetized donor rats with limb outflow returned to the donor rat. Perfusion pressure was monitored. Complete NE (injected intra-arterially) dose-response curves in limbs perfused with donor blood from nine early 1K,1C rats, compared with nine appropriate normotensive control donor rats, indicated unchanged thresholds, 50% effective doses, and maximal responses. Curves in limbs perfused with blood from 10 chronic 1K,1C, compared with 10 appropriate controls, suggested small (P less than 0.02) leftward shifts. Decreases (P less than 0.01) in maximal responses were also observed. Limb resting resistance and minimal resistance (sodium nitroprusside) did not rise, even after 4-5 h of cross-perfusion. These results provide no evidence in early 1K,1C and little evidence in chronic 1K,1C that humoral factors, including ouabainlike inhibitors, evoke physiologically significant inotropic effects in arterioles in vivo.