A unifying hypothesis proposes that brain mechanisms activated by Ang II and high NaCl regulate sympathetic drive and a neurohumoral pathway mediated by endogenous ouabain to modulate cardiovascular function.
Endogenous ouabain and α2 Na+ pumps may play a central mechanistic role in regulating blood pressure and cardiac hypertrophy via modulation of calcium homeostasis and sympathetic activity.
Abstract Reduced smooth muscle (SM)‐specific α2 Na + pump expression elevates basal blood pressure (BP) and increases BP sensitivity to angiotensin II (Ang II) and dietary NaCl, whilst SM‐α2 overexpression lowers basal BP and decreases Ang II/salt sensitivity. Prolonged ouabain infusion induces hypertension in rodents, and ouabain‐resistant mutation of the α2 ouabain binding site (α2 R/R mice) confers resistance to several forms of hypertension. Pressure overload‐induced heart hypertrophy and failure are attenuated in cardio‐specific α2 knockout, cardio‐specific α2 overexpression and α2 R/R mice. We propose a unifying hypothesis that reconciles these apparently disparate findings: brain mechanisms, activated by Ang II and high NaCl, regulate sympathetic drive and a novel neurohumoral pathway mediated by both brain and circulating endogenous ouabain (EO). Circulating EO modulates ouabain‐sensitive α2 Na + pump activity and Ca 2+ transporter expression and, via Na + /Ca 2+ exchange, Ca 2+ homeostasis. This regulates sensitivity to sympathetic activity, Ca 2+ signalling and arterial and cardiac contraction. image
Blaustein et al. (Tue,) conducted a review in Hypertension and heart failure. α2 Na+ pump modulation and endogenous ouabain was evaluated. A unifying hypothesis proposes that brain mechanisms activated by Ang II and high NaCl regulate sympathetic drive and a neurohumoral pathway mediated by endogenous ouabain to modulate cardiovascular function.