Adaptation of the heart to hypertension is associated with maladaptive gap junction connexin-43 remodeling.
We hypothesized that hypertension-related myocardial remodeling characterized by hypertrophy and fibrosis might be accompanied by cell-to-cell gap junction alterations that may account for increased arrhythmogenesis. Intercellular junctions and expression of gap junction protein connexin-43 were analyzed in rat heart tissues from both spontaneous (SHR) and L-NAME model of hypertension. Isolated heart preparation was used to examine susceptibility of the heart to lethal ventricular fibrillation induced by low potassium perfusion. Ultrastructure observation revealed enhanced neoformation of side-to-side type while internalization of end-to-end type (intercalated disc-related) of gap junctions prevailed in the myocardium of rats suffering from either spontaneous or L-NAME-induced hypertension. In parallel, immunolabeling showed increased number of connexin-43 positive gap junctions in lateral cell membrane surfaces, particularly in SHR. Besides, focal loss of immunopositive signal was observed more frequently in hearts of rats treated with L-NAME. There was a significantly higher incidence of hypokalemia-induced ventricular fibrillation in hypertensive compared to normotensive rat hearts. We conclude that adaptation of the heart to hypertension-induced mechanical overload results in maladaptive gap junction remodeling that consequently promotes development of fatal arrhythmias.
Fialová
M
M
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Dlugošová
K
K
Okruhlicová
L
L
Kristek
F
F
Manoach
M
M
Tribulová
N
N
D000222:Adaptation, Physiological; D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism / Q000648:ultrastructure; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007008:Hypokalemia / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D011188:Potassium; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000378:metabolism*
D018031:Connexin 43; D011188:Potassium