High angiotensin II responsiveness is associated with decreased endothelium-dependent relaxation in human arteries

Introduction. Animal studies demonstrated an interaction between angiotensin 11 (Ang 11) responsiveness And endothelium-dependent relaxation (EDR). However, this relation has not been well described in humans. Therefore, we investigated the relation between Ang 11 responsiveness and EDR in isolated human Arteries. Materials and Methods. Segments of the internal mammary artery (IMA) were harvested from 89 patients undergoing coronary bypass surgery. Rings of these segments were exposed in organ bath experiments to metacholine (ME; 10 nmol/L -0.1 mmol/L) after precontraction with phenylephrine (PE; 10 mu mol/L), And secondly to increasing concentrations of Ang 11 (0.1, nmol/L -1 mu mol/L). Results. Patients with the highest contraction to Ang 11 showed the lowest ME relaxation (r=0.312; p=0.003). Angiotensin-converting enzyme (ACE)-inhibition significantly increased Ang 11 sensitivity (p=0.03). This increase was accompanied by a tendency toward decreased EDR (p=0.07). The inverse relation between Ang responsiveness and endothelitium-dependent relaxation could not be explained by an increased tissue or serum ACE-inhibition in patients with a higher endothelium-dependent relaxation. Conclusions. High Ang 11 responsiveness inversely correlates to EDR in IMA's of patients with established coronary Artery disease. Short-term treatment with an ACE-inhibitor increased the response to Ang 11, but had ail adverse effect on EDR.