Proarrythmic Mechanomodulation of Cholinergic Effects in the Right Atrial Structures of Normotensive and Spontaneously Hypertensive Rats

Arterial hypertension (AH) is a leading modifying risk factor for cardiovascular mortality. Systemic or pulmonary AH also serves as a significant factor stimulating the development of atrial fibrillation (AF). The pathophysiological mechanisms underlying the mutually reinforcing AH–AF relationship are multifaceted, caused by structural, biochemical, and electrical remodeling of the atria. About 20% of AF cases owe to the occurrence of ectopic activity in the right atrial (RA) structures, which includes the heart’s natural dominant pacemaker, the sinoatrial node (SAN), and the arrhythmogenic myocardium of the vena cava wall. The mechanisms stimulating the emergence of RA profibrillatory foci in response to AH-induced mechanical exposure remain poorly understood. The aim of this work was to study the proarrhythmic mechanomodulation of the electrophysiological properties of vulnerable zones in the RA myocardium, as well as its susceptibility to cholinergic influences. Experiments were carried out on isolated RA tissue preparations from normotensive Wistar rats (400 ± 50 g, n = 16) and spontaneously hypertensive rats (SHR) (SBP: 180–220 mm Hg, 300 ± 50 g, n = 10), which demonstrated automatic activity and included the SAN, as well as the orifices and distal part of the superior vena cava (SVC). Using the multichannel microelectrode recording technique, the resting potential and spontaneous action potentials (APs) were co-recorded in the atrial and distal parts of the SVC under control conditions, as well as under mechanical loading/stretching accompanied by the action of acetylcholine (ACh). The AP duration in the SVC of hypertensive rats was significantly shorter than in normotensive animals. The frequency of spontaneous APs in the SAN of hypertensive rats was lower than in normotensive controls. The ACh-induced negative chronotropic effect in hypertensive rats was significantly greater than in normotensive animals. Mechanical loading/stretching caused a depolarization (to –60 ± 5 mV), a decrease in AP amplitude, as well as excitation conduction suppression and block in the SVC. The above effects in the SVC of hypertensive rats developed under a significantly weaker mechanical exposure than in Wistar rats. Mechanical loading/stretching increased sinus rhythm in the preparations from normotensive rats (cycle length: –14 ± 3%, n = 16, p < 0.01) but caused its decrease in those from hypertensive rats (+20 ± 9%, p < 0.01). Mechanomodulation enhanced the negative chronotropic effect of ACh. This enhancement was far more pronounced in hypertensive than in normotensive animals: under loading/stretching, ACh suppressed sinus rhythm in 100% of experiments in hypertensive and only in 50% in normotensive rats. Conclusion: under control conditions, the RA myocardium of normotensive and spontaneously hypertensive rats demonstrated different bioelectrical properties and different ACh sensitivity. The SAN and SVC in hypertensive rats were more sensitive to mechanomodulation. Mechanical loading/stretching increased SAN sensitivity to cholinergic stimulation.