Luchner A, Stevens T L, Borgeson D D, Redfield M M, Bailey J E, Sandberg S M, Heublein D M, Burnett J C
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, Minn. 55905, USA.
Hypertension. 1996 Sep;28(3):472-7. doi: 10.1161/01.hyp.28.3.472.
Although angiotensin II (Ang II) has been implicated in the pathophysiology of congestive heart failure, its temporal and regional changes during the development and progression of the disease are poorly defined. Our objective was to assess circulating, renal, cardiac, and vascular Ang II in a canine model of rapid ventricular pacing-induced heart failure that evolves from early left ventricular dysfunction to overt congestive heart failure. Ang II was measured by radioimmunoassay with low cross-reactivity to other angiotensins. Control, early left ventricular dysfunction, and overt congestive heart failure dogs were studied. Early left ventricular dysfunction was characterized by impaired cardiac function, cardiac enlargement, preserved renal perfusion pressure, maintained urinary sodium excretion, and normal plasma renin activity. Overt congestive heart failure was characterized by further impaired cardiac function and cardiac enlargement, reduced renal perfusion pressure, urinary sodium retention, and increased plasma renin activity and plasma Ang II. In early left ventricular dysfunction dogs, renal cortical, renal medullary, ventricular, and aortic Ang II were unchanged, and atrial Ang II was decreased. In overt congestive heart failure dogs, Ang II was increased in the kidney and heart compared with normal dogs and in all tissues compared with early left ventricular dysfunction dogs. The greatest increase in tissue Ang II occurred in the renal medulla. We conclude that early increases in local renal, myocardial, and vascular Ang II do not occur in this model of early left ventricular dysfunction and may even be suppressed. In contrast, increased myocardial and particularly renal Ang II in association with increased circulating Ang II are hallmarks of overt experimental congestive heart failure. These studies provide new insights into the temporal and regional alterations in Ang II during the progression of experimental congestive heart failure.
尽管血管紧张素II（Ang II）与充血性心力衰竭的病理生理学有关，但其在疾病发生和发展过程中的时间和区域变化尚不明确。我们的目的是评估快速心室起搏诱导的心力衰竭犬模型中循环、肾脏、心脏和血管中的Ang II，该模型从早期左心室功能障碍发展为明显的充血性心力衰竭。采用对其他血管紧张素交叉反应性低的放射免疫分析法测定Ang II。对对照组、早期左心室功能障碍组和明显充血性心力衰竭组的犬进行了研究。早期左心室功能障碍的特征是心功能受损、心脏扩大、肾灌注压保持、尿钠排泄维持正常以及血浆肾素活性正常。明显充血性心力衰竭的特征是心功能进一步受损、心脏扩大、肾灌注压降低、尿钠潴留、血浆肾素活性和血浆Ang II升高。在早期左心室功能障碍的犬中，肾皮质、肾髓质、心室和主动脉中的Ang II未发生变化，而心房中的Ang II降低。在明显充血性心力衰竭的犬中，与正常犬相比，肾脏和心脏中的Ang II升高，与早期左心室功能障碍的犬相比，所有组织中的Ang II均升高。组织中Ang II升高幅度最大的是肾髓质。我们得出结论，在这个早期左心室功能障碍模型中，局部肾脏、心肌和血管中的Ang II早期并未升高，甚至可能受到抑制。相比之下，心肌尤其是肾脏中的Ang II升高以及循环中的Ang II升高是明显实验性充血性心力衰竭的标志。这些研究为实验性充血性心力衰竭进展过程中Ang II的时间和区域变化提供了新的见解。
