digoxin and Hypertension--Renovascular

We assessed the role of putative circulating ouabainlike factor(s) on in vivo arteriolar function in rats with very early (less than 7 days; mean, 3 days) and chronic (greater than 4 weeks) benign, one-kidney, one clip (1K1C) hypertension. Thus, we measured vascular responses in vasodilated (nitroprusside or adenosine), vascularly isolated, innervated hindlimb vascular beds of chloralose-anesthetized 1K1C rats perfused with their own blood at 1 ml/min. Complete norepinephrine dose-response curves in 8 rats with chronic and 28 with early 1K1C hypertension, compared with appropriate normotensive control rats, showed unchanged thresholds and ED50 values. Magnitude of ouabain-induced leftward shifts of the norepinephrine dose-response curve in 18 rats with chronic and 21 with early 1K1C hypertension, compared with appropriate normotensive control rats, was unchanged. Blockade of neural uptake of norepinephrine by desimipramine (10(-7) M) in 8 1K1C rats did not alter these results. These findings provide no evidence in this form and these stages of hypertension that humoral ouabainlike inhibitors of the Na+-K+ pump evoke physiologically significant inotropic effects in arterioles in vivo. It is possible, however, that induction of vascular Na+-K+-adenosine triphosphatase by circulating inhibitors modified the vascular responses to norepinephrine and ouabain in these rats.

Topics: Animals; Arteries; Arterioles; Blood Proteins; Cardenolides; Desipramine; Digoxin; Hindlimb; Hypertension, Renovascular; Male; Norepinephrine; Ouabain; Rats; Rats, Inbred Strains; Saponins; Sodium-Potassium-Exchanging ATPase

A circulating factor with digoxin immunoreactivity has been demonstrated. Elevated levels of this substance appear to be present after volume expansion and salt loading, and in some forms of hypertension. The potentially causative role for this factor in hypertension can be demonstrated by the normalization of blood pressure after antidigoxin antibody infusions in low-renin and sodium-dependent hypertension. The possibility that renal excretory defects may be the initiating event to elevate endogenous digoxin is suggested by studies with normotensive humans and monkeys with renal disease. In the latter case cardiovascular deficits were noted that were analogous to those detected in renal hypertensive monkeys with elevated endogenous digoxin. Considered together, these results suggest the existence of a natriuretic and hypertensive substance that plays a role in body fluid homeostasis and blood pressure regulation.

Topics: Animals; Antibodies; ATPase Inhibitory Protein; Blood Proteins; Blood Volume; Cardenolides; Cardiac Glycosides; Cross Reactions; Digoxin; Dogs; Humans; Hypertension; Hypertension, Renovascular; Ion Channels; Kidney; Macaca mulatta; Natriuretic Agents; Organ Size; Pressoreceptors; Proteins; Saponins