title: Aldosterone nongenomically worsens ischemia via protein kinase C-dependent pathways in hypoperfused canine hearts.
abstract: Rapid nongenomic actions of aldosterone independent of mineralocorticoid receptors (MRs) on vascular tone are divergent. Until now, the rapid nongenomic actions of aldosterone on vascular tone of coronary artery and cardiac function in the in vivo ischemic hearts were not still fully estimated. Furthermore, although aldosterone can modulate protein kinase C (PKC) activity, there is no clear consensus whether PKC is involved in the nongenomic actions of aldosterone on the ischemic hearts. In open chest dogs, the selective infusion of aldosterone into the left anterior descending coronary artery (LAD) reduced coronary blood flow (CBF) in the nonischemic hearts in a dose-dependent manner. Also, in the ischemic state that CBF was decreased to 33% of the baseline, the intracoronary administration of aldosterone (0.1 nmol/L) rapidly decreased CBF (37.4+/-3.8 to 19.3+/-5.2 mL/100 g/min; P<0.05), along with decreases in fractional shortening (FS) (8.4+/-0.7 to 5.4+/-0.4%; P<0.05) and lactate extraction rate (LER) (-31.7+/-2.9 to -41.4+/-3.7%; P<0.05). The decrease in CBF was reproduced by the infusion of bovine serum albumin-conjugated aldosterone. Notably, these aldosterone-induced deteriorations of myocardial contractile and metabolic functions were blunted by the co-administration of GF109203X, an inhibitor of PKC, but not spironolactone. In addition, aldosterone activated vascular PKC. These results indicate that aldosterone nongenomically induces vasoconstriction via PKC-dependent pathways possibly through membrane receptors, which leads to the worsening of the cardiac contractile and metabolic functions in the ischemic hearts. Elevation of plasma or cardiac aldosterone levels may be deleterious to ischemic heart disease through its nongenomic effects.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujita
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Akio
authors.initials: A
authors.lastname: Hirata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Wakeno
authors.forename: Masafumi
authors.initials: M
authors.lastname: Myoishi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okuda
authors.forename: Akiko
authors.initials: A
authors.lastname: Ogai
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Okada
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsukamoto
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Koyama
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D014661:Vasoconstriction
chemical_list: D000450:Aldosterone; D011493:Protein Kinase C