Od pressure (16). In addition to previous reports, in early stage of Ang II-dependent hypertension, PRR and COX-2 were reported to be augmented in the renal medullary tissues and to mediate vasoconstriction effects of Ang II (55). In renal inner medullary cells, activation of PRR upregulates COX-2 expression by means of MAPK-ERK1/2 signaling pathway, and (PRR and COX-2) was shown to colocalize in interstial and intercalated cells. Downregulation of PRR attenuated the boost in COX-2 expression, suggesting a function of PRR in regulating COX-2, independent of Ang II pathway (56). Taken collectively, these studies suggest that COX-2 contributes for the hypertension independently of the renin or Ang II levels. In transgenic rats (TGRCyp1a1-Ren2)) with Ang II dependent hypertension, selective COX-2 inhibition led to pronounced decreases in GFR, suggesting that the enhanced intrarenal COX-2 counteracts the vasoconstrictor action of Ang II inside the kidney and play an essential role in preserving GFR. On the other hand, inhibition of COX-2 decreased arterial blood stress, indicating that the systemic COX-2 derived prostanoids have vasoconstrictive action and contributes towards the development of hypertension (57). In Cyp1a1-Ren2 rats, inhibition of COX-2 with blockade of neuronal nitric oxide synthase (nNOS) increased renal vascular resistance, demonstrating the renal vasodilator effects of COX-2 (57). Activation of RAS activity through elevated ROS generation through chronic Ang II infusion and in salt sensitive hypertension leads to upregulation of COX-2 (58). Elevated ROS activity could alter the connection between COX-2 and Ang II from antagonistic to cooperative with regard for the blood pressure effects (59).Author Manuscript Author Manuscript Author Manuscript Author Manuscript7.2. Part of AT2R and COX-2 in hypertension AT2 receptor mediated response to hypertension includes regulation of eicosanoids. Arachidonic acid in the kidney is processed by cytochrome p450 CYP2C to make 20-HETE which acts as a vasoconstrictor and inhibitor of sodium transport whilst CYP 2J produces a group of molecules called EETs (epoxyeicosatrienoic acids) which are vasodilators as well as inhibitors of sodium transport (60). 20-HETE promotes the development of hypertension but also appears to become protective against glomerular injury even though EETs market vasodilation in an NO and COX-2 independent mechanism (60).Apolipoprotein E/APOE Protein Gene ID As demonstrated by Bautista et al, inside the setting of kidney injury the AT2 receptor triggers a vasodilator effect that is mediated by elevated production of epoxyeicosatrienoic acids (EETs) and decreased production of 20HETE (61).Galectin-9/LGALS9 Protein MedChemExpress 20-HETE production inside the rat kidney is meanwhile mediated by the AT2 receptor and 20-HETE has been shown to contribute towards the vasoconstrictor response to Ang II (62).PMID:24834360 Both sets of compounds also have effects on natriuresis. EETs prevent sodium retention and their blockade leads to elevated blood stress in a method dependent on serine/threonine protein phosphatase (60). In a single study, inhibition of arachidonic acid metabolism prevents renal vasodilation when COX inhibition with indomethacin does not, suggesting that the vasodilator impact is dependent on CYP 450 arachidonic metabolism but not on COX (61). Even so, Brouwers et al showed that in hypertensive rats treated with an ACE inhibitor, the AT2 receptor agonist C21 induced a vasodilator response that wasFront Biosci (Schol Ed). Author manuscript; obtainable in PMC 2017 June 01.Quadri et al.Pagepar.
