Angiotensin II-induced Hypertension is Reduced by Deficiency of P-selectin Glycoprotein Ligand-1

Abstract

Identification of inflammatory mediators that regulate the vascular response to vasopressor molecules may aid in the development of novel therapeutic agents to treat or prevent hypertensive vascular diseases. Leukocytes have recently been shown to be capable of modifying blood pressure responses to vasopressor molecules. The purpose of this study was to test the hypothesis that deficiency of the leukocyte ligand, Psgl-1, would reduce the pressor response to angiotensin II (Ang II). Mice deficient in Psgl-1 (Psgl-1−/−) along with wild-type (WT) controls were treated for 2 weeks with a continuous infusion of Ang II. No differences in blood pressure between the groups were noted at baseline, however after 5 days of Ang II infusion, systolic blood pressures were higher in WT compared to Psgl-1−/− mice. The pressor response to acute administration of high dose Ang II was also attenuated in Psgl-1−/− compared to WT mice. Chimeric mice with hematopoietic deficiency of Psgl-1 similarly showed a reduced pressor response to Ang II. This effect was associated with reduced plasma interleukin-17 (IL-17) levels in Psgl-1−/− mice and the reduced pressor response was restored by administration of recombinant IL-17. In conclusion, hematopoietic deficiency of Psgl-1 attenuates Ang II-induced hypertension, an effect that may be mediated by reduced IL-17.

Understanding the Connection Between Common Stroke Comorbidities, Their Associated Inflammation, and the Course of the Cerebral Ischemia/Reperfusion Cascade

“…Moreover, elevated levels of chemokines, e.g., RANTES, were found in the serum of hypertensive patients ( 138 , 139 ). The expression of some other adhesion molecules, e.g., P-selectin in platelets and endothelium and its antigen, PSGL-1 in the endothelium, may also take place through the action of the pro - hypertensive angiotensin II on the AT 1 R receptor (angiotensin II type 1 receptor) ( 140 ). Also immune cells residing in the brain – microglia/macrophages are sensitive to ongoing hypertension.…”

Adaptive Immunity in Hypertension

“…Interestingly, this effect resulted in reduced plasma IL-17 level in Psgl-1 −/− mice compared with wild type (WT) animals. The administration of recombinant IL-17 restored the reduced response to Ang II [93]. IL-17 expression is regulated by Tri-partite motif (TRIM) 21 [94].…”

Retinol-binding protein 4 is closely correlated to blood pressure level and E/A in untreated essential hypertension patients

“…The occurrence and development of hypertension are closely related to inflammatory response (12)(13)(14). Previous studies show that inflammatory reaction can promote proliferation, migration and differentiation of vascular cells, leading to damage of cardiac tissue stroma and collagen deposition, vascular dysfunction, myocardial hypertrophy, myocardial fibrosis and ventricular remodeling, causing deterioration of myocardial relaxation and myocardial compliance, and eventually resulting systolic and diastolic dysfunction (15).…”