Synchrotron radiation microangiography is a powerful tool for assessing adverse changes in pulmonary vessel density associated with primary pulmonary hypertension (PH). Congestive heart failure (CHF) leads to a `secondary' onset of PH, yet it is unknown whether secondary PH is also associated with reduced vessel density. This study utilized synchrotron radiation to assess both pulmonary vessel density and endothelial function in a Dahl rat model of CHF with secondary PH. High salt-fed Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were anesthetized and microangiography was performed to assess the pulmonary vessel density and vascular responses to (i) sodium nitroprusside (5.0 µg kg(-1) min(-1)), (ii) acetylcholine (3.0 µg kg(-1) min(-1)) and (iii) ET-1A receptor blockade, BQ-123 (1 mg kg(-1)). Dahl-S rats developed CHF and secondary PH as evident by endothelial dysfunction, impaired vasodilatory responses to acetylcholine, enhanced vasodilatory responses to BQ-123 and extensive pulmonary vascular remodeling. Consequently, the pulmonary vessel density was adversely reduced. Interestingly, the etiology of secondary PH manifests with structural and functional changes that are comparable with that previously reported for primary PH. One important discrepancy, however, is that ET-1 modulation of pulmonary vessels is most striking in vessels with a diameter range of 100-200 µm in secondary PH, in contrast to a range of 200-300 µm in primary PH. Such discrepancies should be considered in future studies investigating primary and secondary forms of PH.
Keywords: endothelin-1; microangiography; nitric oxide; secondary pulmonary hypertension.