title: The role of a humoral Na+,K+-ATPase inhibitor in regulating precapillary vessel tone.
abstract: In this review, we first present chronologically our evidence suggesting that a circulating Na+,K+-ATPase and Na+-K+ pump inhibitor in part regulates the mechanical activity of the muscle in the cardiovascular system. We then present the relevant findings from other laboratories. The evidence from our laboratories includes the observations that local hyperkalemia decreases small-vessel resistance and local hypokalemia increases small-vessel resistance and that these responses can be blocked by ouabain, a potent Na+,K+-ATPase inhibitor. Myocardial Na+,K+-ATPase and vascular Na+-K+ pump activities are decreased in animals with experimental low-renin hypertension, vascular Na+-K+ pump activity is decreased in animals following acute volume expansion, and these changes are associated with bioassay evidence for a Na+-K+ pump inhibitor in the plasma. The inhibitor appears to come from, or be influenced by, the anteroventral third ventricle (AV3V) area of the brain. It produces electrogenic depolarization of the vascular smooth-muscle cell and may inhibit norepinephrine uptake by adrenergic nerve terminals. The evidence from other laboratories includes the observations that there is (a) a pressor and vascular sensitizing agent in the plasma of animals and patients with low-renin hypertension, (b) reduced Na+-K+ pump activity in the leukocytes of some patients with essential hypertension, and (c) a Na+,K+-ATPase and Na+-K+ pump inhibitor in the plasma of some patients with essential hypertension.
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000201:enzymology; D002320:Cardiovascular Physiological Phenomena; D002412:Cations / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000235:genetics; D006977:Hypertension, Renal / Q000503:physiopathology; D007962:Leukocytes / Q000201:enzymology; D008564:Membrane Potentials; D008833:Microcirculation / Q000502:physiology*; D009129:Muscle Tonus; D009206:Myocardium / Q000201:enzymology; D009411:Nerve Endings / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000097:blood / Q000502:physiology; D012083:Renin / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000502:physiology; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology; D014655:Vascular Resistance
chemical_list: D002412:Cations; D014639:Vanadium; D014638:Vanadates; D012083:Renin; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D009638:Norepinephrine