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Each of ten steers taken for 9 weeks to 12,700 ft. (Mt. Evans, Colorado) showed a marked increase in pulmonary artery (PA) pressure. Three animals had PA pressures above 90 mm Hg and one developed right heart failure. The bovine species is remarkable for the severe pulmonary hypertension which develops during chronic hypoxia rather than for an excessive PA pressure response to acute hypoxia. The rate at which the pulmonary hypertension developed at 12,700 ft. was extremely rapid compared to that at 10,000 ft. Therefore, not only the duration of the hypoxic stimulus but also its severity determine the response. The severity of the stimulus was augmented by the absence of a sustained increase in ventilation at high altitude. The pressure rise with acute hypoxia during the control period at low altitude and the dramatic fall in PA pressure when oxygen was administered at high altitude provided evidence for hypoxia-induced pulmonary vasoconstriction as an important mechanism in bovine pulmonary hypertension. Submitted on June 6, 1962

This study examines the hypothesis that susceptibility of cattle to high-altitude pulmonary hypertension and heart failure (high mountain disease) is genetically transmitted. Eight offspring of cattle recovered from high mountain disease were considered "susceptible." Eleven offspring of healthy cattle residing at high altitude were considered "resistant." At the resident altitude of 1,524 m, 10-day-old susceptible calves had higher pulmonary arterial pressures than did resistant calves (34 vs.21 mmHg), but at 90 days of age the pressures for the two groups were similar (26 vs. 24 mmHg). After 64 days of exposure to an altitude of 3,048 m, the susceptible calves (87 +/- 7 (SE) vs. 40 +/- 3 mmHg). By 124 days at 3,048 m, all susceptible but none of the resistant calves had developed heart failure. The results indicated that susceptibility to pulmonary hypertension at high altitude was inherited. Susceptible cattle may provide a useful model of human hypoxic pulmonary hypertension.

Right ventricular hypertrophy produced in rats exposed to 10% oxygen for 3 weeks resulted in a ninefold increase in atriopeptin immunoreactivity (APir) and a 160-fold increase in atriopeptin messenger RNA (AP mRNA) in the right ventricular myocardium. A small but significant increase in left ventricular APir and AP mRNA was also present, probably representing the interventricular septum. Right atrial APir was decreased by 50%, but left atrial APir was not different from normoxic controls. Purification of ventricular tissue extracts by high-performance liquid chromatography revealed primarily the high molecular weight prohormone. The development of right ventricular hypertrophy and right ventricular APir content followed a similar time course, each evident at 7 days of hypoxia and reaching a plateau at 14 days. Hypoxia followed by normoxia caused right ventricular APir to fall to control levels within 3 days, despite persistent right ventricular hypertrophy. This data demonstrates that hypoxia can reversibly induce extra-atrial expression of atriopeptin synthesis in the cardiac ventricle.