Circulating AGT is synthesized in the liver, but AGT is also produced in tissues such as the brain, large arteries, kidney, heart, and adipose tissue, where it is hydrolyzed by extravascular renin or other proteases to ANG I or directly to ANG II family of proteins, and the fact that some serpin proteins regulate angiogenesis led to the discovery of the antiangiogenic properties of AGT and des AGT.No specic AGT or des AGT receptors have been detected, but both proteins bind to AT and AT receptors at their micromolar plasma concentrations. AGT does not affect the expression of angiogenic Losartan potassium growth factors in vivo; instead, it directly suppresses proliferation of endothelial cells and induces their apoptosis that may reect blood vessels destabilized by the absence of AGT in glial cells surrounding brain capillaries. Local conditions may determine whether the antiangiogenic properties of AGT and des AGT prevail over the proangiogenic effects of ANG II.In summary, due to the dual effects of RAS hormones, local conditions affecting their synthesis and clearance rate, the production and activity of the converting proteases, and their receptormediated signaling pathways would determine whether an antiangiogenic or an angiogenic condition prevails.ACE inhibitors and AT receptor Cabazitaxel blockers, which are among the most widely prescribed drugs for blood pressure control, lower ANG II generation and action and increase renin levels, accelerating AGT cleavage into antiangiogenic des AGT and ANG. RASBK interactions are essential for balancing blood pressure and illustrate the sophisticated local and systemic interactions inuencing the nal angiogenic response.The plasma KKS is known as the contact system, because originally the only known mechanism for its activation was contact with articial, negatively charged surfaces.However, it is now recognized that the contact system is activated physiologically at the cell membrane, leading to the generation of small peptides and proteins with effects on blood coagulation, inammation, pain, natriuresis, blood pressure, vascular permeability, and angiogenesis. Most plasma prekallikrein circulates bound to HK, and on the endothelial cell surface HK serves as its main binding site. Upon binding to the endothelial cell surface via HK, prekallikrein is converted to kallikrein by prolylcarboxypeptidase. BK stimulates angiogenesis by activating two G proteincoupled receptor subtypes, B and B, but while the B receptor is constitutively expressed, the B receptor is upregulated following tissue damage, ischemia, and inammation. Notably, BK also stimulates endothelial cell growth and permeability by increasing B receptormediated VEGF expression in broblasts, whereas the B receptor contributes to the proangiogenic action of BK by increasing bFGF synthesis in endothelial cells. BK also induces the phosphorylationactivation of VEGFR, which can promote eNOS activation. Of importance, BK is rapidly inactivated in the intravascular compartment, and it disappears completely after a single passage through the pulmonary circulation.Domain can be cleaved by plasma kallikrein to produce the angiogenic nonapeptide bradykinin. BK can then be processed by angiotensinconverting enzyme. Various peptidases, including ACE, metabolize BK to generate smaller peptides that have no known effect on angiogenesis. Pharmacological inhibitors of ACE, both by reducing ANG II levels and by blocking the degradation of BK, help control cardiovascular diseases, including hypertension and myocardial infarction.