Are Sildenafil Derivatives Useful Even in Unborn Males?

Abstract

See related article, pp 753–758 As noted by Romo et al,1 the past decade has witnessed an increased incidence, in the general population, of intrauterine growth retardation (IUGR), currently averaged at 5.13% of all newborns. An elegant survey by Hutter et al2 subsequently highlighted the major causes of intrauterine hypoxia often associated with IUGR. Those authors additionally argued in favor of an important role for intrauterine hypoxia-induced alteration of gene expression in the increased incidence of risk factors in premature cardiovascular diseases at later life stages.2 In the present study, Bourque et al3 provide experimental evidence toward a role for the precursor of endothelin-1 (ET-1), big-ET-1, as a new stressor in aged male rats that experienced prenatal hypoxia-induced IUGR. Interestingly, the authors demonstrated a vascular hyper-responsiveness to big-ET-1 and a 2-fold reduction in nitric oxide (NO)–dependent physiological antagonism of the precursor’s contractile properties in vessels derived from aged male but not female rats. Furthermore, an orally available mixed ETA/ETB antagonist, tezosentan,4 attenuated the hypertensive state of aged IUGR …