Differential changes in left and right ventricular adenylyl cyclase activities in congestive heart failure

Abstract

The status of beta-adrenergic receptors and adenylyl cyclase in crude membranes from both left and right ventricles was examined when the left coronary artery in rats was occluded for 4, 8, and 16 wk. The adenylyl cyclase activity in the presence of isoproterenol was decreased in the uninfarcted (viable) left ventricle and increased in the right ventricle subsequent to myocardial infarction. The density of beta1-adrenergic receptors, unlike beta2-receptors, was reduced in the left ventricle, whereas no change in the characteristics of beta1- and beta2-adrenergic receptors was seen in the right ventricle. The catalytic activity of adenylyl cyclase was depressed in the viable left ventricle but was unchanged in the right ventricle. In comparison to sham controls, the basal, as well as NaF-, forskolin-, and 5'-guanylyl imidodiphosphate [Gpp(NH)p]-stimulated adenylyl cyclase activities were decreased in the left ventricle and increased in the right ventricle of the experimental animals. Opposite alterations in the adenylyl cyclase activities in left and right ventricles from infarcted animals were also seen when two types of purified sarcolemmal preparations were employed. These changes in adenylyl cyclase activities in the left and right ventricles were dependent on the degree of heart failure. Furthermore, adenosine 3',5'-cyclic monophosphate contents were higher in the right ventricle and lower in the left ventricle from infarcted animals injected with saline, isoproterenol, or forskolin in comparison to the controls. The results suggest differential changes in the viable left and right ventricles with respect to adenylyl cyclase activities during the development of congestive heart failure due to myocardial infarction.

Impaired beta-adrenergic response and decreased L-type calcium current of hypertrophied left ventricular myocytes in postinfarction heart failure

“…Right ventricular hypertrophy was also detected: the right ventricle/body weight ratio in postinfarction animals was increased by 123% compared to sham animals ( Table 1). The extent of increase in both wet and dry lung and right ventricle weights observed here corresponds to that reported for large infarcts in rats with reduced ventricular function and increased left ventricular diastolic pressure, which are clear signs of heart failure (3,4,6,7,10,17,26). As expected, we also detected ascites, a typical sign of heart failure in most of the postinfarction animals.…”

“…The model of chronic infarct in rats is characterized by the presence of hypertrophy and, in the case of large infarcts, of heart failure (3)(4)(5)(6)(7)(8), and represents a clinically relevant model of left ventricle dysfunction (9). The decrease in the mechanical performance in this model includes not only the loss of myocardium caused by the infarct, but also decreased contractility and response to ß-adrenergic stimulation of the remaining hypertrophied myocardium (3,5,8,10).…”

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,ItoK+currents, and [Ca2+]itransients

“…Left ventricular free wall infarct sizes of hearts used in our studies were 47.5 Ϯ 2.6% (range 34.4-64.0%). Hearts with infarct sizes Ͻ30% were not included in our analysis because small infarcts are not associated with significant hemodynamic changes (30,47). As summarized in Table 1, MI was associated with global and cellular hypertrophy.…”

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

“…This procedure eliminates artifacts due to ischemia or apoptosis and thus, deals with reactive hypertrophy. 24 After LV infarction, RV hypertrophy, an important determinant in the prognosis of heart failure, 25 is also observed 26,27 and might be independent of mechanical factors. 28 One week after surgery, V C ( Figure 1A) and C m (see below) were similar in myocytes isolated from post-MI and shamoperated rats, indicating that cellular hypertrophy had not occurred at this stage.…”