Disease relevance of PD 123319

• However, ratios of heart weight to body weight were higher in coarctation (4.95 +/- 0.8) or coarctation plus PD 123319 (4.52 +/- 0.5) than in sham animals (3.6 +/- 0.4; P < .005 and .05, respectively) [1].
• Thus, combined treatment with losartan + PD 123319 proved more effective in attenuating the reflex increase in plasma epinephrine concentration during hypoglycemia than either of the two AT receptor antagonists given alone [2].
• Furthermore, PD 123319 attenuates the development of hypertension in salt-loaded rats neonatally treated with capsaicin, indicating that the AT2 receptor contributes to the increase in blood pressure [3].
• PD 123319 did not affect calpain I or II up-regulation in the infarcted myocardium, but decreased interstitial fibrosis [4].
• These data indicate that EXP 3174 and PD 123319 inhibit thirst evoked by centrally injected AII, but not that caused by extracellular dehydration [5].

High impact information on PD 123319

• L-arginine (L-ARG) given intravenously or interstitially enhanced net fluid absorption and cGMP formation, which were completely blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine methylester (L-NAME), but not by the specific AT2 receptor antagonist, PD-123319 (PD) [6].
• In nonfailing hearts, 69 +/- 4% of binding sites were blocked by the subtype-2-specific inhibitor PD 123319 and were therefore classified as AT2; 33 +/- 5% were blocked by the subtype-1-specific inhibitor DUP 753 and thus classified as subtype 1 [7].
• Moreover, treatment with the selective AT1 antagonist CV-11974 before injury significantly decreased the formation of neointima in only WT mice, whereas treatment with the selective AT2 antagonist PD-123319 before injury had no effects in both animal groups [8].
• Valsartan, a specific AT1 receptor antagonist inhibited Ang II binding, whereas PD 123319, an AT2 receptor antagonist did not [9].
• This stimulatory effect of Ang II on Erk1 and Erk2 activities was potentiated by blockade of AT2 receptors with (S)-1-[4-(dimethylamino)-3-methylphenyl]methyl-5-(diphenylacetyl)- 4, 5,6,7-tetrahydro-1H-imidazo[4,5-C]pyridine-6-carboxylic acid (PD 123319, 1 microM) [10].

Chemical compound and disease context of PD 123319

• The effects of intracerebroventricularly (i.c.v.) administered angiotensin nonpeptide receptor ligands losartan (DuP-753) and PD-123319 and their interactions with Ang II were examined on acute anoxic hypoxia in male mice [11].
• Results showed that losartan and PD-123319 exerted antihypoxic effects including increased latency to convulsive seizures and survival time and pretreatment with both drugs enhanced Ang II-increased survival time [11].

Biological context of PD 123319

• AT2 receptor blockade with PD 123319 did not change the renal blood flow while it increased the diuresis and natriuresis [12].
• In contrast, AngII activation of the symport was blocked by nanomolar AT2 receptor antagonist PD 123319 [13].
• The putative AT2 receptor antagonist PD 123319 inhibited 30 to 40% of AngII-induced vasoconstriction, whereas CGP 42112 had no effect in either group [14].
• In contrast, PD 123319 abolished the upregulation of NBC-1 mRNA and protein but had no effect on NHE-1 upregulation [15].
• Saralasin and Exp 6803, but not PD 123319, lowered blood pressure in renal hypertensive rats following intravenous administration [16].

Anatomical context of PD 123319

• Microinjection into the anterior hypothalamic area of the selective type 2 angiotensin II receptor antagonist PD 123319 did not affect blood pressure or heart rate in NaCl-sensitive spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)[17]
• Binding studies on adrenal slices, on cell membranes and on cell suspensions were performed using [125I]AII and specific analogs for AT1 (Losartan) and AT2 (PD 123319) receptors [18].
• Treatment of the endothelial cells with PD-123319, a type 2 receptor antagonist, prevented the angiotensin II-dependent increase in nitric oxide synthase mRNA, protein levels, and nitric oxide production [19].
• Determination of isometric tension in fetal aortas showed potentiated ANG II-induced contraction by treatment with the selective AT(2)R antagonist PD-123319, demonstrating the presence of functional AT(2)Rs that mediate reduced force development in vascular SMC [20].
• PD-123319 alone (10(-5) M) showed no AT(1)-like action to constrict microperfused DVR or increase pericyte [Ca(2+)](i) [21].

Associations of PD 123319 with other chemical compounds

• Furthermore, the AT2 receptor agonist N-alpha-nicotinoyl-Tyr-Lys-(N-alphaCBZ-Arg)-His-Pro-Ile-OH (CGP42112A) (10-50 nM) caused significant decreases in neuronal Erk1 and Erk2 activities, which were abolished by PD 123319 (1 microM) and by the PP2A inhibitor okadaic acid (3 nM) [10].
• DuP 753, an AT1 receptor antagonist, blocked both effects induced by Ang 1-7, whereas PD 123319, an AT2 receptor antagonist, did not block the stimulatory effect [22].
• The effects of ANG II and of losartan plus ANG II on aortic cGMP content were both blocked by cotreatment with the AT2 receptor antagonist PD 123319 [23].
• Angiotensin II AT2 receptor stimulation extends the upper limit of cerebral blood flow autoregulation: agonist effects of CGP 42112 and PD 123319 [24].
• Although no functional role for the PD 123319-sensitive subclass has yet been identified, the Dup 753/Exp 6803-sensitive subclass plays an important role in mediating inositol phosphate metabolism, vascular contractile activity, and blood pressure regulation [16].

Gene context of PD 123319

• In contrast, the AT2 receptor analogues PD-123319 and CGP-42112 at concentrations < 10(-6) M had no effect on ANG II binding [25].
• The residual constrictor effect observed during AT1 receptor blockade and sensitive to PD 123319 appears to be mediated by a non-AT1 receptor [14].
• The selective AT2 receptor ligand, CGP 42112A, antagonized AII-induced [3H]-thymidine incorporation with an IC50 of 6.3 +/- 1.3 microM while the AT2/AT1B receptor antagonist, PD 123319, was found to be almost inactive (IC50 > 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)[26]
• Co-incubation with both losartan and PD-123319 resulted in a decrease of ERK and p38 activities in cardiomyocytes [27].
• The binding of [125I]Sar1-angiotensin II was completely displaced by the AT1 antagonist losartan but not by the AT2 receptor ligand PD 123319, confirming the expression of angiotensin II AT1 receptors in NCI-H295 cells [28].

Analytical, diagnostic and therapeutic context of PD 123319

• The AT2 receptor antagonist PD 123319 had no effect on increases in systemic arterial and hindquarters perfusion pressure in response to AngII [29].
• Intravenous infusion of PD 123319 was more effective than bolus injection [30].
• In control rats, intraventricular administration of losartan prevented the pressor and renal vascular resistance responses to intraventricular injection of ANG II, in a dose-dependent manner (P < 0.05), while intraventricular injection of PD 123319 was ineffective [31].
• We measured the effect of the AT2 receptor selective ligand PD 123319 on cerebral blood flow (CBF) in rats, using laser-doppler flowmetry [32].
• Given at 100 micrograms/5 microliters i.c.v., the angiotensin AT2-selective receptor antagonist, PD 123319, did not reduce hemodynamic responses to electric stimulation [33].

References