title: Potassium supplementation reduces cardiac and renal hypertrophy independent of blood pressure in DOCA/salt mice.
abstract: We have demonstrated previously that deoxycorticosterone acetate (DOCA)/salt induces cardiac hypertrophy and left ventricular dysfunction independent of blood pressure (BP) in 1-renin gene mice. Because these mice also develop hypokalemia and metabolic alkalosis caused by mineralocorticoid excess, we investigated whether correcting hypokalemia by dietary potassium supplementation would prevent the DOCA/salt-induced cardiac hypertrophy, cardiac dysfunction, and electrocardiographic changes in normotensive, 1-renin gene and hypertensive, 2-renin gene mice. All mice were studied after 5 weeks of DOCA and salt administration. Potassium was given by adding 0.4 or 0.6% KCl to the drinking water. Our results show that correction of hypokalemia and metabolic alkalosis prevents cardiac hypertrophy and normalizes cardiac function without affecting BP in normotensive, 1-renin gene mice. In hypertensive, 2-renin gene mice, potassium supplementation induces a significant decrease in BP. The decrease in BP and correction of kalemia are associated with a significant but partial correction of cardiac hypertrophy. In both group of mice, electrocardiographic alterations were measured after administration of DOCA/salt, which could be corrected by potassium supplementation. Thus, these results show that correction of hypokalemia and metabolic alkalosis does prevent the development of cardiac hypertrophy and normalizes cardiac function independent of BP in normotensive, 1-renin gene mice that receive excess mineralocorticoid and salt. In 2-renin gene, hypertensive mice, potassium supplementation also prevents the development of cardiac hypertrophy, but the effect cannot be separated from the decrease in BP.
authors.affiliation: Division of Nephrology, University Hospital, Lausanne, Switzerland.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Domenighetti
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedrazzini
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006332:Cardiomegaly / Q000139:chemically induced / Q000517:prevention & control*; D018797:Cell Cycle Proteins; D003900:Desoxycorticosterone; D004032:Diet; D004562:Electrocardiography; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D007008:Hypokalemia / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D012083:Renin / Q000235:genetics; D012965:Sodium Chloride; D014166:Transferases
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C473112:Ren2 protein, mouse; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C466095:Kctd11 protein, mouse; D014166:Transferases; D012083:Renin; D011188:Potassium