ABSTRACT
We determined parameters of elasticity of peripheral arteries in patients with heart failure (HF) including those with pulmonary arterial hypertension. We also investigated pulmonary artery responses to vasoconstricting factors in vitro. Reactivity of the aorta and carotid artery was studied on the model of experimental HF. Lowering of elasticity of small arteries progressed with worsening of HF functional class and increase of pulmonary arterial hypertension. In the genesis of pulmonary hypertension definite role played elevated constrictor response of pulmonary artery to endothelin 1 at the background of dysfunction of endothelial ETB receptors. Endothelial dependent reactivity of the aorta and carotid artery was impaired and their constrictor effect augmented.
Subject(s)
Elasticity , Heart Failure/physiopathology , Hypertension, Pulmonary/physiopathology , Vascular Resistance/drug effects , Comorbidity , Disease Progression , Endothelin B Receptor Antagonists , Endothelin-1/pharmacology , Endpoint Determination , Heart Failure/epidemiology , Humans , Hypertension, Pulmonary/epidemiology , Pulmonary Artery/physiopathology , Receptor, Endothelin B/drug effects , Vasoconstrictor Agents/pharmacologyABSTRACT
Despite obvious participation of endothelins in pathogenesis of heart failure therapeutic approaches to the use of endothelin receptor antagonists remain to be elucidated. Experimental heart failure caused by prolonged infusion of norepinephrine is associated with diminished endothelin induced coronary constricting effect of stimulation of ET(A) receptors and inversion of coronary dilating effect of stimulation of these receptors. The latter effect is mediated by smooth muscle ET(B)-receptors and is indicative of functional derangement of vascular control by endothelial cells. The use of selective ET(A)-antagonist is effective on early stages of heart failure while on later stages administration of nonselective ET(AB)-antagonist produces more pronounced effect.
