NANOMOLAR OUABAIN AUGMENTS CAFFEINE-EVOKED CONTRACTIONS IN RAT ARTERIES

Chronic parenteral administration of ouabain to normal rats raises pla sma ouabain concentrations to low nanomolar levels and induces hyperte nsion [C. M. Yuan, P. Manunta, J. M. Hamlyn, S. W. Chen, E. Bohen, J. Yeun, F. J. Haddy, and M. B. Pamnani. Hypertension 22: 178-187, 1993 a nd see also M. P. Blaustein. Am. J. Physiol. 264 (Cell Physiol. 33): C 1367-C1387, 1993]. To determine whether rat arteries are sensitive to these low ouabain levels, we tested the effects of various ouabain con centrations on caffeine-evoked contractions (CEC) in rat aortic and sm all mesenteric artery rings. CEC amplitude was used as a measure of th e sarcoplasmic reticulum (SR) Ca2+ content. Ouabain increased CEC in a ortic as well as mesenteric artery rings, but the effects in the aorta were difficult to quantitate because the CEC were often oscillatory. Mesenteric artery, under control conditions and after sensitization wi th 10-30 nM phenylephrine (PE), exhibited biphasic ouabain dose-CEC re sponse curves. Low concentrations of ouabain (0.1-10 nM) caused small significant increases in CEC, but a further effect was observed only w ith greater-than-or-equal-to 10 muM ouabain. PE shifted the ouabain do se-response curve toward lower ouabain concentrations; conversely, oua bain shifted the PE dose-response curve toward lower PE concentrations . It appears that nanomolar concentrations of ouabain can influence va scular responsiveness to vasoconstrictors. We conclude that rat vascul ar smooth muscle contains both high- and low-affinity ouabain receptor s, possibly corresponding to Na+ pumps with alpha3- and alpha1-subunit isoforms, respectively. Physiological regulation of the high-affinity isoform by endogenous ouabain may, indirectly, modulate SR Ca2+ conte nt and vascular reactivity by influencing cytosolic Na+ and thus Na+-C a2+ exchange and cytosolic Ca2+.