Myocardial beta-adrenergic reactivity in patients with resistant arterial hypertension and obstructive coronary atherosclerosis

Background. Long-term activation of adrenergic receptors in patients with hypertension (HTN) has detrimental long-term effects leading to left ventricular hypertrophy (LVH) and subsequent development of heart failure. In case of sympathetic overactivation, the representation and sensitivity of beta1-adrenergic receptors (β1-AR) decreases, and the main β-adrenergic regulation is mediated via β2-AR. However, their sensitivity can also change, which affects the possibility of adequate inotropic support of the contractile function of the heart. It remains relevant to clarify the inotropic function of cardiomyocytes in HTN patients, to assess the mechanisms of the development and severity of heart remodeling and neurohumoral regulation. Objective is to study the inotropic potential of β-AR stimulation in isolated trabeculae of the right atrium in patients with resistant HTN and obstructive coronary atherosclerosis. Design and methods. The study included 17 people with resistant HTN combined with coronary artery disease (CAD) referred for coronary artery bypass grafting due to multivessel atherosclerotic coronary lesions. The exclusion criteria were: symptomatic hypertension, chronic kidney disease stage C3-C4, absence of CAD. Myocardial contractility was studied ex vivo on isolated muscle preparations (trabeculae of the right atrial appendage) obtained during the intravenous cannulation in patients connected to a cardiopulmonary bypass machine during coronary artery bypass grafting. The inotropic response of trabeculae was assessed in the isometric mode. To influence β1and β2-AR, agonists were used against the background of preceding α-AR blockade. Results. The correlation analysis showed that the inotropic response of trabeculae to β1-AR stimulation in patients with resistant hypertension negatively correlates with the myocardial mass (MM) of the LV (r = –0,52; p = 0,04) and the average daily diastolic blood pressure (BP) (r = –0,64; p = 0,009), and with β2-AR stimulation with the dimensions of the posterior wall of the LV (PWL) (r = –0,50; p = 0,04) and the dimensions of the left atrium (LA) (r = –0,54; p = 0,03). A direct correlation was found in patients with preserved left ventricular (LV) ejection fraction (EF) between the inotropic response of isolated trabeculae to β1-AR stimulation and the LVEF value (r = 0,64; p = 0,02). When dividing patients into groups according to the level of adrenoreactivity, i. e. according to the reaction of the isolated myocardium to β1,2-AR agonists, it was found that in patients with a strong reaction the level of average daily, average daily systolic blood pressure and pulse blood pressure was lower. Conclusion. As a result of the study, a relationship was found for the first time between changes in the inotropic potential of β1and β2-AR stimulation of the right atrial myocardium and BP levels and morpho-functional changes in the heart. This is of significant importance for understanding the mechanisms of formation of hypertensive myocardial pathology and the role of sympathetic hyperactivation in the development of these processes. The obtained results indicate that cardiac remodeling in patients with a combination of coronary heart disease and hypertension is associated with the characteristics of β-AR activity according to inotropic stimulation data.

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