Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active á1B-adrenoceptors

The regulatory function of á1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant á1B-adrenoceptor (CAMá1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30 percent in CAMá1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na+/K+-ATPase activity nor the expression of á1 and á2 subunit isoforms was changed in CAMá1B-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac á1B-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.

Protective effects of astragaloside Ⅳ on hypertrophy induced by angiotensinⅡ in primary cultured cardiomyocytes of neonatal rats / 中国药理学通报

Aim To investigate the protective effects and mechanism of astragaloside Ⅳ on hypertrophy induced by angiotensinⅡ(AngⅡ)in primary cultured cardiomyocytes of neonatal rats.Methods Cardiomyo-cytes were incubated with AngⅡ to establish the hypertrophy model of primary cultured cardiomyocytes in neonatal rats.AST 10 mg?L-1 or 20 mg?L-1 were added with AngⅡ simultaneously to observe its protective effects on cardiomyocytes.The diameter and the total protein content of cardiomyocyte were measured.The intracellular free calcium concentration([Ca2+]i),activity of sarcoplasmic reticulum Ca2+-ATPases(SERCA)and activity of calcineurin(CaN)were determined.Results Compared with control group,diameter and total protein content of cardiomyocyte induced by AngⅡ were increased significantly,which were inhibited by AST 10 mg?L-1 and 20 mg?L-1,respectively(P