Blockade of brain "ouabain" prevents sympathoexcitatory and pressor responses to high sodium in SHR.
The effects of blockade of brain "ouabain" by central infusion of antibody Fab fragments, which bind ouabain and brain "ouabain" with high affinity, on sodium-sensitive hypertension were studied in spontaneously hypertensive rats (SHR) from 5 to 9 wk of age on high- or regular sodium diet. The Fab fragments or, in controls, gamma-globulins were infused intracerebroventricularly via osmotic minipump. Blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) and their responses to air stress and to the alpha 2-adrenoceptor agonist guanabenz intracerebroventricularly were recorded in conscious rats at 9 wk. In control SHR but not Wistar-Kyoto rats (WKY), high sodium further increased resting mean arterial pressure (171 +/- 3 vs. 141 +/- 4 mmHg in control SHR on regular sodium) and potentiated excitatory and inhibitory responses of BP, HR, and RSNA to air stress and intracerebroventricular guanabenz, respectively. These effects of high sodium were all prevented by intracerebroventricular Fab fragments. In SHR on regular sodium or WKY on either diet, the Fab fragments had no effects on resting BP or responses to air stress and guanabenz. We conclude that similar to Dahl salt-sensitive rats, in SHR, a sodium-induced increase in brain "ouabain" is responsible for the decreased sympathoinhibition and increased sympathoexcitation and thus the exacerbation of hypertension. Brain "ouabain" appears not to be involved in the development of hypertension in SHR on regular sodium intake.
Huang
B S
BS
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Leenen
F H
FH
D000388:Air; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D004039:Diet, Sodium-Restricted; D006143:Guanabenz / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors*; D010812:Physical Stimulation; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects*
D007140:Immunoglobulin Fab Fragments; D010042:Ouabain; D006143:Guanabenz