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The aim of this study was to establish how thromboxane receptors (TP) respond to the increase in levels of plasma thromboxane observed in both cardiac (cardiomyopathy, ischaemic heart disease and pulmonary hypertension) and vascular disease (atherosclerosis of coronary artery disease and accelerated atherosclerosis of saphenous vein grafts). 2. The agonist radioligand (125)I-BOP, bound rapidly to TP receptors in normal human cardiovascular tissue, displaying high affinity in left ventricle (K(D) 0.23 +/- 0.06 nM, B(max) 28.4 +/- 5.7 fmol mg(-1) protein) and reversibility with a t(1/2) of 10 min (n = five individuals +/- s.e.mean). 3. In the heart, TP receptor density in the right ventricle of primary pulmonary hypertensive patients were significantly increased (66.6 +/- 6 fmol mg(-1) protein) compared to non-diseased right ventricle (37.9 +/- 4.1 fmol mg(-1) protein, n = six individuals +/- s.e.mean, P<0.05). 4. In diseased vessels, TP receptor densities were significantly increased (3 fold in the intimal layer) in atherosclerotic coronary arteries, saphenous vein grafts with severe intimal thickening (n = 8-12 individuals, P<0.05) and aortic tissue (n=5 - 6 individuals, P<0.05), compared with normal vessels. 5. Losartan, tested at therapeutic doses, competed for (125)I-BOP binding to human vascular tissue, suggesting that some of the anti-hypertensive effects of this AT(1) receptor antagonist could also be mediated by blocking human TP receptors. 6. The differential distribution of TP receptors in the human cardiovascular system and the alteration of receptor density, accompanying the increase in endogenous thromboxane levels in cardiovascular disease, suggest that TP receptors represent a significant target for therapeutic interventions and highlights the importance for the development of novel selective antagonist for use in humans.
Katugampola et al. (2001) studied this question.