Vascular Endothelin and Angiotensin Receptors Regulation in Inflammatory Arterial Disorders

Sammanfattning: The present thesis is aimed to examine the hypothesis that the degree of vascular inflammation correlates with the expression of vascular endothelin and angiotensin receptors. The receptor changes were studied in subcutaneous resistance arteries in patients with different degrees of ischemic heart disease (IHD). In addition, patients with giant cell arteritis (GCA) were also investigated because of the massive inflammatory activity in affected vessels. For functional studies of the resistance arteries, sensitive myographs were used. Receptor protein levels were measured quantitatively using immunohistochemistry or western blot. Main results: 1. Patients with suspected acute coronary syndrome (angina pectoris) have increased expression of AT1 and ETB receptors in vascular smooth muscle cells (VSMC) in subcutaneous resistance arteries. 2. The level of the up-regulation of contractile AT1 and ETB receptors depends on the degree of underlying IHD. The phenomenon is also correlated to the level of the systolic blood pressure. 3. Temporal arteries from patients with GCA have up-regulation of AT1 and ETB receptors in the VSMC in the medial layer of the arterial wall. The degrees of up-regulation of ETB receptors are directly correlated to the degree of the systemic inflammatory response (CRP). 4. Accompanying lymphocytic infiltrates as well as giant cells in the lesions of the temporal arteries express high immunostaining of endothelin-1 and up-regulation of ETB and AT1 receptors as well. 5. De novo expression of tissue endothelin-1 was observed in the VSMC in the medial layer as well in the neointima in affected arteries. 6. ETB receptors mediate contraction of subcutaneous resistance arteries in ischemic heart disease. The present thesis demonstrated that there is increased ETB and AT1 receptor expression in VSMC in ischemic heart disease and in GCA which correlates with the degree of inflammation.