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J Appl Physiol (March 31, 2005). doi:10.1152/japplphysiol.01337.2004
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Submitted on November 30, 2004
Accepted on March 20, 2005

Thromboxane inhibition reduces an early stage of chronic hypoxia-induced pulmonary hypertension in piglets

Candice D Fike*, Yongmei Zhang, and Mark R Kaplowitz

* To whom correspondence should be addressed. E-mail: cfike{at}wfubmc.edu.

The pulmonary vasoconstrictor, thromboxane, may contribute to the development of pulmonary hypertension. Our objective was to determine if a combined thromboxane synthase inhibitor/receptor antagonist, terbogrel, prevents pulmonary hypertension and the development of aberrant pulmonary arterial responses in newborn piglets exposed to 3 days hypoxia. Piglets were maintained in room air (control) or 11% O2 (hypoxic) for 3 days. Some hypoxic piglets received terbogrel, 10 mg/kg po bid. Pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured in anesthetized animals. A cannulated artery technique was used to measure responses to acetylcholine. Pulmonary vascular resistance for terbogrel-treated hypoxic piglets was almost one-half the value of untreated hypoxic piglets but remained greater than values for control piglets. Dilation to acetylcholine in preconstricted pulmonary arteries was greater for terbogrel-treated hypoxic than for untreated hypoxic piglets, but was less for pulmonary arteries from both groups of hypoxic piglets than for control piglets. Terbogrel may ameliorate pulmonary artery dysfunction and attenuate the development of chronic hypoxia-induced pulmonary hypertension in newborns.




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