Central infusions of benzamil prevent/reverse salt-induced hypertension in genetic models of salt-sensitive hypertension. Benzamil acts by blockade of ion--presumably sodium--channels. In the present study, we assessed in Dahl salt-sensitive (S) rats on high salt intake whether these channels mediate increases in brain "ouabain" and, thereby, hypertension. Intracerebroventricular (icv) infusion...

OBJECTIVES We investigated whether chronic ouabain treatment changes the vasoconstrictor responses induced by electrical field stimulation (EFS) in endothelium-denuded rat superior mesenteric arteries and a possible role of neuronal nitric oxide (NO). METHOD Mesenteric arteries from untreated and ouabain-treated rats (approximately equal to 8.0 microg/kg per day, for 5 weeks) were used in thi...

REPLY: Fürstenwerth (12a) notes that my “Perspectives” on endogenous ouabain (EO) (2) 1) didn’t mention the use of ouabain as a therapeutic and antihypertensive agent (true; see last paragraph); 2) didn’t consider the view that “(EO) is not ‘ouabain’” (21) [I cited an earlier version (32) and the refutation (24); my article (2) was published online 4 days before Lewis and colleagues’ (21); see ...

Tian, Jiang, Xiaohua Gong, and Zijian Xie. Signal transducing function of Na-K-ATPase is essential for ouabain’s effect on [Ca]i in rat cardiac myocytes. Am J Physiol Heart Circ Physiol 281: H1899–H1907, 2001.—We showed before that Na-K-ATPase is also a signal transducer in neonatal rat cardiac myocytes. Binding of ouabain to the enzyme activates multiple signal pathways that regulate cell grow...

Using fura 2-loaded vessels, we tested whether ouabain modulates endothelial cytoplasmic calcium concentration ([Ca(2+)](CYT)) in rat descending vasa recta (DVR). Over a broad range between 10(-10) and 10(-4) M, ouabain elicited biphasic peak and plateau [Ca(2+)](CYT) elevations. Blockade of voltage-gated Ca(2+) entry with nifedipine did not affect the response to ouabain mitigating against a r...

Delayed afterdepolarizations and triggered activity were evoked in focal areas of myocardium in vivo by local exposure of endocardium to ouabain by means of a catheter electrode system capable of recording monophasic action potentials (MAPs) and delivering ouabain to the recording site. MAPs were recorded from the septum and the posterior wall of the left ventricle with silver-silver chloride e...

Angiotensin (Ang) II stimulates secretions of aldosterone and an endogenous ouabain-like steroid (EO) from bovine adrenal zona glomerulosa (BAG) cells. The BAG cell sodium pump, a possible target of EO, affects aldosterone secretion although little is known about this pump. Here, we describe the effects of Ang II on the characteristics of this transporter and steroid secretions. Under serum-fre...

The ion transporter Na-K-ATPase functions as a cell signal transducer that mediates ouabain-induced activation of protein kinases, such as ERK. While Na-K-ATPase composed of the alpha(1)-polypeptide is involved in cell signaling, the role of other alpha-isoforms (alpha(2), alpha(3), and alpha(4)) in transmitting ouabain effects is unknown. We have explored this using baculovirus-directed expres...

Ouabain acutely depolarizes most types of cells through inhibition of electrogenic Na+,K+ pumping and is a useful tool with which to study conditions that affect electrogenic pumping. Intracellular recording techniques were used with neurons of the guinea pig myenteric plexus/longitudinal muscle preparation exposed to ouabain. Of 35 S neurons exposed to ouabain (1 microM), 15 were hyperpolarize...

Blaustein, Mordecai P., Jin Zhang, Ling Chen, and Bruce P. Hamilton. How does salt retention raise blood pressure? Am J Physiol Regul Integr Comp Physiol 290: R514–R523, 2006; doi:10.1152/ajpregu.00819.2005.—A critical question in hypertension research is: How is long-term blood pressure controlled? Excessive NaCl ingestion or NaCl retention by the kidneys and the consequent tendency toward pla...