Abstract <p>Arterial hypertension (AH) is a leading modifying risk factorfor cardiovascular mortality. Systemic or pulmonary AH also servesas a significant factor stimulating the development of atrial fibrillation(AF). The pathophysiological mechanisms underlying the mutuallyreinforcing AH–AF relationship are multifaceted, caused by structural,biochemical, and electrical remodeling of the atria. About 20% ofAF cases owe to the occurrence of ectopic activity in the rightatrial (RA) structures, which includes the heart’s natural dominantpacemaker, the sinoatrial node (SAN), and the arrhythmogenic myocardiumof the vena cava wall. The mechanisms stimulating the emergenceof RA profibrillatory foci in response to AH-induced mechanicalexposure remain poorly understood. The aim of this work was to studythe proarrhythmic mechanomodulation of the electrophysiologicalproperties of vulnerable zones in the RA myocardium, as well asits susceptibility to cholinergic influences. Experiments were carriedout on isolated RA tissue preparations from normotensive Wistarrats (400 ± 50 g, <i>n</i> = 16) andspontaneously hypertensive rats (SHR) (SBP: 180–220 mm Hg, 300 ±50 g, <i>n</i> = 10), which demonstratedautomatic activity and included the SAN, as well as the orificesand distal part of the superior vena cava (SVC). Using the multichannelmicroelectrode recording technique, the resting potential and spontaneous actionpotentials (APs) were co-recorded in the atrial and distal partsof the SVC under control conditions, as well as under mechanicalloading/stretching accompanied by the action of acetylcholine (ACh).The AP duration in the SVC of hypertensive rats was significantlyshorter than in normotensive animals. The frequency of spontaneousAPs in the SAN of hypertensive rats was lower than in normotensivecontrols. The ACh-induced negative chronotropic effect in hypertensiverats was significantly greater than in normotensive animals. Mechanicalloading/stretching caused a depolarization (to –60 ± 5 mV), a decreasein AP amplitude, as well as excitation conduction suppression andblock in the SVC. The above effects in the SVC of hypertensive ratsdeveloped under a significantly weaker mechanical exposure thanin Wistar rats. Mechanical loading/stretching increased sinus rhythmin the preparations from normotensive rats (cycle length: –14 ±3%, <i>n</i> = 16, <i>p</i> &lt; 0.01) but caused its decreasein those from hypertensive rats (+20 ± 9%, <i>p</i> &lt;0.01). Mechanomodulation enhanced the negative chronotropic effectof ACh. This enhancement was far more pronounced in hypertensive thanin normotensive animals: under loading/stretching, ACh suppressedsinus rhythm in 100% of experiments in hypertensive and only in50% in normotensive rats. Conclusion: under control conditions,the RA myocardium of normotensive and spontaneously hypertensiverats demonstrated different bioelectrical properties and differentACh sensitivity. The SAN and SVC in hypertensive rats were moresensitive to mechanomodulation. Mechanical loading/stretching increasedSAN sensitivity to cholinergic stimulation.</p>