Lung vascular smooth muscle as a determinant of pulmonary hypertension at high altitude

Abstract

The pulmonary hypertensive response to chronic hypoxia varies markedly among mammalian species. An explanation for this variability was sought by exposing seven species to hypobaric hypoxia (PB equal to 435 mmHg) for 19-48 days. Control animals were studied at 1,600 m (PB equal to 630 mmHg). The pulmonary hypertension that developed varied in the following order of decreasing severity: calf and pig (severe); rat and rabbit (moderate); sheep, guinea pig, and dog (mild). Right ventricular hypertrophy developed in proportion to the elevation in right ventricular systolic pressure. These interspecies variations in response were not correlated with the degree of arterial hypoxemia, degree of polycythemia, elevation in heart rate, or postnatal age. However, the medial thickness of the small pulmonary arteries in control animals was highly correlated with the development of pulmonary hypertension and right ventricular hypertrophy in hypoxic animals. Thus, the amount of lung vascular smooth muscle inherent within each species is a major determinant of the pulmonary hypertensive response to high altitude and contributes to the interspecies variability in this response.

Using guinea pigs in studies relevant to asthma and COPD

“…Perhaps as an adaptation to this environment, guinea pigs have a remarkably low mean arterial blood pressure (30-50mmHg) relative to that of humans and other commonly used species (80-100mmHg) and are thus far more susceptible to cardiovascular collapse, as in anaphylaxis [2,141,292]. The guinea pig pulmonary circulation also responds only modestly to hypoxia, with a slight elevation in pulmonary arterial pressure relative to the response of humans, pigs or rats [304]. The extensive peptidergic afferent innervation of the bronchial vasculature and the axon reflex also makes the guinea pig particularly susceptible to a profound neurogenic inflammation, with coincident leukocyte recruitment, bronchospasm, vasodilatation, increased airway epithelial and endothelial permeability and mucus secretion.…”

Efecto Del Ketoprofeno Sobre La Presión Arterial Pulmonar en Terneros Jersey Sometidos a Hipoxia De La Altura.

“…Los valores de PAPm obtenidos en la altura (Cuadro 1) estuvieron elevados y similares a los obtenidos por Tucker et al (1975) y Will et al (1975) en condiciones similares. Para Ames (2001), estos valores de PAPm están dentro del rango aceptable para introducir ganado bovino en la altura (PAPm < 41 mm Hg) pudiendo considerarse como un buen indicador.…”

The effect of hypertonic saline dextran solutions on hypoxic pulmonary vasoconstriction in anaesthetised piglets

“…Piglets where chosen because they exhibit one of the greatest pulmonary vasoconstriction responses to hypoxia [5] and previous experiments have demonstrated linear P/Q relationships [7]. However, HPV shows a large interindividual and interspecies variability relative to vascular reactivity [10] Therefore, no statistical comparison was performed between the two groups at baseline as the hypoxic pressor response was more marked in the dextran group than in the NaCl with dextran group ( fig.…”

“…It was hypothesised that these two different plasma expanders would have different effects on hypoxic pulmonary vasoconstriction (HPV), and thereby modify gas exchange. Piglets were chosen because they exhibit the greatest pulmonary vasoconstriction response to hypoxia [5]. In this study, pulmonary haemodynamics were evaluated by multipoint P/Q (mean pulmonary arterial pressure (PAP)-LAP/Q) plots, which provide quantitative characterisation of the PVR/Q relationships [6].…”