Hemodynamic mechanism of ventricular hypertrophy in hypertension.

Arterial hemodynamic assessments with technique of spectral analysis can obtain complete hemodynamic parameters including steady and pulsatile components. The steady parameters include arterial pressure (AP), heart rate, cardiac output, stroke volume and total peripheral resistance (TPR). Parameters of pulsatile hemodynamics are characteristic impedance (Zc), arterial compliance (Cm) and pulse wave reflection (Pb) etc. Studies of ventricular hypertrophy (VH) and arterial hemodynamics have disclosed several important findings. Hypertension in spontaneously hypertensive rat (SHR) and human subjects causes functional abnormalities in the resistance and Windkessel vessels. The extent of VH in SHR and hypertensive subjects was not correlated with AP and TPR, but positively correlated with pulsatile hemodynamic factors such as Zc and Pb. Many antihypertensive and vasodilators were capable of reducing the AP, but did not improve the VH. We have also investigated the effects of vasodilatory agents such as nifedipine (a calcium channel blocker), propranol (a non-selective β-adrenergic blocker) and atenol (a selective β-adrenergic inhibitor) on the arterial hemodynamics and VH. In addition, the effects of acute and chronic nitric oxide (NO) deprivation with Nω-nitro-L-arginine methyl ester (L-NAME) on the arterial hemodynamics and VH were evaluated. We compared the endothelium-dependent and -independent vasodilation to acetylcholine, sodium nitroprusside and S-nitroso-N-acetylpenicillanine and the endothelium-dependent or -independent vasoconstriction to norepinephrine and phenylephrine between SHR and normotensive Wistar Kyoto strain. In SHR with long-term administration of L-NAME, VH was associated with decreases in left ventricular cGMP and nitrate/nitrite accompanying increase in collagen content. Coadministration of NO precursor L-arginine improved the VH and fibrosis. In VH caused by long-term L-NAME, the LW/BW ratio, total number, numerical density and size of cardiomyocytes were correlated well with both steady and pulsatile hemodymanics. Aortic stiffness has significant impact on the cardiovascular risks. We simulated aortic stiffness by applying silicon gel embedding of the abdominal and/or thoracic aorta. Aortic stiffness did not affect the blood pressure and the steady hemodynamics. It caused VH associated with increases in the pulsatile hemodynamics. The extent of VH (LVW/BW, total number, numerical density, size of cardiomyocytes and collagen volume fraction) was correlated with the pulsatile hemodynamics (impedance, pulse wave velocity and wave reflection). The finding further supports the contention that blood pressure is not the determinant of VH. The ventricular afterload is the major cause of VH. The hemodynamic consequences of ovariectomy (Ovx), menopause and estrogen replacement were investigated. Ovx increased body weight, LVW/BW ratio, Zc and Pb, but decreased Cm. These changes were reversed by estrogen replacement. For steady hemodynamics, Ovx did not much alter the systolic, mean and diastolic pressure. The pulse pressure was slightly elevated. There was large increase in TPR. Again, these changes were reversed by estrogen supplement. The implication of these findings was that menopause tends to exert vasoconstrictory effects on the resistance and Windkessel vessels. On the contrary, estrogen possesses a vasodilatory influence on the systemic vessels.