Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension.
Rabbits were rendered hypertensive by suprarenal coarctation of the abdominal aorta. Seven days later, endothelium-dependent and endothelium-independent vascular relaxations were examined in vascular rings taken from hypertensive (thoracic aorta, carotid artery) and normotensive (abdominal aorta) regions. Relaxation of phenylephrine-contracted rings in response to endothelium-dependent agonists (acetylcholine, A23187) was impaired, compared with that in sham-operated and intact controls, in regions exposed to the elevated blood pressure (i.e., above the coarctation). Responses to acetylcholine and A23187 in the abdominal aorta, below the coarctation, were not altered. The diminished endothelium-dependent responses in the thoracic aorta were not affected by pretreatment with the cyclooxygenase inhibitor indomethacin. In contrast to acetylcholine and A23187, responses to the endothelium-independent agonist nitroprusside were not attenuated in vessels from hypertensive regions, indicating that the defect occurred in the endothelium. The EC50 for acetylcholine-induced relaxations of thoracic aorta correlated significantly with mean arterial pressure above the coarctation, indicating that the extent to which endothelium-dependent relaxation is impaired is in proportion to the degree of blood pressure elevation. This study suggests that the diminished relaxations by endothelium-dependent agonists is a local response to the elevation of blood pressure and is not due to a circulating factor.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology; D001013:Aorta, Thoracic / Q000503:physiopathology; D001017:Aortic Coarctation / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D000001:Calcimycin / Q000494:pharmacology; D002339:Carotid Arteries / Q000503:physiopathology; D004727:Endothelium / Q000502:physiology*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine; D011817:Rabbits
D009599:Nitroprusside; D010656:Phenylephrine; D000001:Calcimycin; D000109:Acetylcholine; D007213:Indomethacin