Pulmonary Arterial Hypertntion Causes Disregultion of Systemic Circulation via Supressesion of Baroceptor Control of the Heart Rhytm

Pulmonary arterial hypertension (PAH) is characterized byan increase of a pressure in the pulmonary circulation; PAH is accompaniedby activation of the sympathetic (SNS) and the renin-angiotensin-aldosteronesystem (RAAS). However, PAH-associated changes in baroreceptor regulationof systemic circulation, which is tightly interwoven with SNS andRAAS, have not been studied. The baroreceptor response (BRR) wasstudied in a chronic monocrotaline (MCT) model of PAH in rats (Wistar,290 ± 30 g, 2–4 months). Phenylephrine as an agonist of α1-adrenergicreceptor and sodium nitroprusside as NO donor were gradually administeredto chronically catheterized, non-anesthetized control animals and animalswith PAH (4 weeks after MCT administration) to induce vasomotorresponses. Mean arterial pressure and heart rate (HR) were recordedunder the action of vasoactive compounds alone or under the actionof vasoactive compounds in presence of angiotensin-II (ATII), atropine.The parameters characterizing baroreceptor change in HR includingmaximal and minimal heart rate (HR_max, HR_min), reflextachycardia (T_BRR) and bradycardia (B_BRR),range (A_BRR) and the baroreceptor response sensitivityindex (SI_BRR) were calculated. A significantdecrease in HR_max, T_BRR,A_BBR (but not B_BRR), aswell as the sensitivity index of BRR was observed in rats with PAH.ATII induces significant and different changes in the BRR parametersin control rats and in rats with PAH if administered 4 weeks afterthe start of the experiment. In rats with PAH, ATII causes lesspronounced changes in HR_max, T_BRR,and B_BRR than in control animals. ATII insignificantlyaffects parasympathetic component of the baroreceptor reflex inrats with PAH. Thus, at least in the MCT-mediated model in rats,PAH significantly deteriorates the baroreceptor regulation of HR.This effect manifests in a decrease in the range and sensitivityof the baroreceptor response. Also, PAH unequally affects the sympatheticand parasympathetic control of the baroreceptor regulation of HR.On the other hand, ATII exhibits weak ability to alter BRR in ratswith HAP. In conclusion, PAH leads to a disfunction of immediate,reflex mechanisms HR and systemic circulation control.