Tissue remodeling of rat pulmonary arteries in recovery from hypoxic hypertension

Abstract

The reversibility of tissue remodeling is of general interest to medicine. Pulmonary arterial tissue remodeling during hypertension induced by hypoxic breathing is well known, but little has been said about the recovery of the arterial wall when the blood pressure is lowered again. We hypothesize that tissue recovery is a function of the oxygen concentration, blood pressure, location on the vascular tree, and time. We measured the changes of blood pressure, vessel lumen, vessel wall thicknesses, and opening angle of each segment of the blood vessel at its zero-stress state after step changes of the oxygen concentration in the breathing gas. The zero-stress state of each vessel is emphasized because it is important to the analysis of stress and strain and in morphometry. Experimental results are presented as histories of tissue parameters after step changes of the oxygen level. Tissue characteristics are examined under the hypothesis that they are linearly related to changes in the local blood pressure. Under this linearity hypothesis, each aspect of the tissue change can be expressed as a convolution integral of the blood pressure history with a kernel called the indicial response function. It is shown the indicial response function for rising blood pressure is different from that for falling blood pressure. This difference represents a major nonlinearity of the tissue remodeling process of the blood vessels.indicial response function ͉ blood vessel opening angle at zero-stress state ͉ nonlinearity of tissue remodeling I t is well known that blood flow in pulmonary arteries becomes hypertensive when an animal breathes a gas the oxygen concentration of which is lower than that of normal sea level air. It is also known that hypertension leads to hypertrophy in blood vessels, and returning to normal blood pressure mitigates the symptom. The question is whether the processes of hypertrophy and recovery are symmetric. Considerable data on the building up of the lung tissue due to pulmonary hypertension have been obtained (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Some data on recovery from hypertension are also given in refs. 1, 4, and 5. These studies considered neither the zero-stress state, which is characterized by an opening angle of the blood vessels, nor the elastic moduli of the blood vessel walls. The significance of the zero-stress state and the change of Young's modulus were recognized later (8,10,11,(15)(16)(17)(18)(19).So far as we are aware, there has been no study on the recovery of the zero-stress state of a vascular tissue that was subjected to hypertension for some time but was returned to the normal condition later. Recovery can be expected to be a complex function of space, time, stress, and strain. The objective of this article is to clarify these points. Materials and MethodsAnimals. Ninety-two male Sprague-Dawley rats (Harlan, San Diego), Ϸ3 months old, body weight 300-350 g, raised in normal air at sea level, were used. These rats were cared for 1 week or more after arrival at the vivari...

The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension

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Bioreactor for the Long-Term Culture of Lung Tissue

“…Maintain perfusion pressures within normal rodent physiological values, with a pulmonary artery pressure of less than 15–30mmHg (16). …”

Pulmonary vascular mechanics: important contributors to the increased right ventricular afterload of pulmonary hypertension

“…Another important characteristic of HPH that is different from severe PH is its reversibility. It has been shown in many studies that if allowed to recover in normoxic conditions, subjects will undergo a reverse remodeling in PAs and a decrease of Ppa, with a reduction in Hct as well (Rabinovitch et al , 1981; Liu, 1997; Tozzi et al , 1998; Riley et al , 2000; Li et al , 2004; Ooi et al , 2010; Tabima et al , 2012). In terms of vascular mechanics, the recovery process is accompanied by reduced proximal PA stiffening and reduced distal PA narrowing (Ooi et al , 2010; Tabima et al , 2012), which then significantly reduces the RV afterload.…”