Remodeling In Chronic Hypertension Research Articles

Hypertension and atrial fibrillation: Evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model

Hypertension accounts for more atrial fibrillation (AF) than any other predisposing factor. The purpose of this study was to characterize the time course, extent, and electrostructural correlation of atrial remodeling in chronic hypertension. Thirty-two sheep were studied: 21 with induced "one-kidney, one-clip" hypertension and 11 controls. Sequential closed-chest electrophysiologic studies were performed in 12 conscious animals (6 hypertensive, 6 controls) to evaluate progressive remodeling over 15 weeks. Additional atrial structural/functional analyses were performed in 5 controls and at 5, 10, and 15 weeks of hypertension (five per time point) via histology/cardiac magnetic resonance imaging to correlate with open-chest electrophysiologic parameters. The hypertensive group developed a progressive increase in mean arterial pressure (P <.001). Mean effective refractory periods were uniformly higher at all time points (P <.001). Progressive biatrial hypertrophy (P = .003), left atrial dysfunction (P <.05) and greater AF inducibility were seen early with increased inflammation from 5 weeks of hypertension. In contrast, significant conduction slowing (P <.001) with increased heterogeneity (P <.001) along with increased interstitial fibrosis resulted in longer and more fractionated AF episodes only from 10 weeks of hypertension. Significant electrostructural correlation was seen in conduction abnormalities and AF inducibility with both atrial inflammation and fibrosis. Hypertension is associated with early and progressive changes in atrial remodeling. Atrial remodeling occurs at different time domains in chronic hypertension with significant electrostructural correlation of the remodeling cascade. Early institution of antihypertensive treatment may prevent formation of substrate capable of maintaining AF.

946 Left atrial remodeling in chronic hypertension during pregnancy

946 Left atrial remodeling in chronic hypertension during pregnancy

Insulin-like growth factoristimulates elastin synthesis by bovine pulmonary arterial smooth muscle cells

Insulin-like growth factor I stimulates mitogenesis in smooth muscle cells, and upregulates elastin synthesis in embryonic aortic tissue. Increased smooth muscle elastin synthesis may play an important role in vascular remodeling in chronic pulmonary hypertension. Therefore, we studied the effect of IGF-I on elastin and total protein synthesis by pulmonary arterial smooth muscle cells in vitro. Tropoelastin synthesis was measured by enzyme immunoassay, and total protein synthesis was measured by [ 3H]-leucine incorporation. In addition, the steady-state levels of tropoelastin mRNA were determined by slot blot hybridization. Incubation of confluent cultures with various concentrations of IGF-I resulted in a dose-dependent stimulation of elastin synthesis, with a 2.4-fold increase over control levels at 1000 ng/ml of IGF. The increase in elastin synthesis was reflected by a stimulation of the steady-state levels of tropoelastin mRNA. We conclude that IGF-I has potent elastogenic effects on vascular smooth muscle cells, and speculate that it may contribute to vascular wall remodeling in chronic hypertension.