Central administration of PD 123319 or EXP-3174 inhibits effects of angiotensin II

Widdop, RE; Gardiner, Sheila M.; Kemp, P.A.; Bennett, T.

doi:10.1152/ajpheart.1993.264.1.h117

Cited by 23 publications

(21 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study indicates that PD 123319 in concentrations greater than 0.5 Mm cross-reacts with the ATIB receptor subtype (De Gasparo et al, 1995). In rat renal mesangial cells, Ernsberger et al (1992) (Widdop et al, 1993a) and the angiotensin II-mediated drinking response in rats (Rowland et al, 1992) are both blocked by PD 123319. In contrast, the structurally related AT2 antagonist, PD 123177, was without effect on the intracerebroventricular administration of angiotensin II (Widdop et al, 1993b;Rowland et al, 1992).…”

Section: Discussionmentioning

confidence: 98%

Angiotensin II receptors involved in the enhancement of noradrenergic transmission in the caudal artery of the spontaneously hypertensive rat

Cox

Story

Ziogas

1996

British J Pharmacology

View full text Add to dashboard Cite

1 The effects of the AT, receptor antagonist losartan and the AT2 receptor antagonist PD 123319, on actions of angiotensin II in isolated caudal arteries of spontaneously hypertensive (SH) and age-matched normotensive (Wistar-Kyoto) rats were compared.2 Angiotensin II (0.1-3 gM) produced concentration-dependent increases in perfusion pressure in artery preparations from both SH and Wistar-Kyoto (WKY) rats, the maximal increase in the SH rat being significantly greater than the increase in WKY rats. The increase in perfusion pressure in preparations from both strains of rats was prevented by losartan (0.1 /M) and unaffected by PD 123319 (0.1 uM), indicating that the vasoconstrictor action of angiotensin II is subserved by AT1 receptors.3 Angiotensin II (0.1-3 pM) produced concentration-dependent enhancement of both stimulationinduced (S-I) efflux of [3H]-noradrenaline and stimulation-evoked vasoconstrictor responses in isolated preparations of caudal artery from both SH and WKY rats, in which the noradrenergic transmitter stores had been labelled with [3H]-noradrenaline. The maximum enhancement of S-I efflux produced by angiotensin II (1 pM) was significantly greater in artery preparations from WKY rats than in preparations from SH rats, whereas the maximum enhancement of stimulation-evoked vasoconstrictor responses was greater in preparations from SH rats than in those from WKY rats. 4 In artery preparations from both WKY and SH rats, the AT1 angiotensin II receptor antagonist, losartan (0.01 and 0.1 pM), reduced or abolished the enhancement of both S-I efflux and vasoconstrictor responses by 1 pM angiotensin II. 5 The combination of 0.01 pM losartan and 0.1 IM angiotensin II enhanced both the S-I efflux and stimulation-evoked vasoconstrictor response in caudal artery preparations from WKY rats, whereas 0.1 UM angiotensin alone was ineffective. The AT2 receptor antagonist PD 123319 (0.01 and 0.1 pM) prevented the enhancement of both S-I efflux and stimulation-evoked vasoconstrictor responses by the combination of angiotensin II and losartan. 6 In contrast to findings in WKY preparations and those previously obtained for arteries from another normotensive strain (Sprague-Dawley), in artery preparations from SH rats there was no synergistic interaction between losartan and angiotensin II. Rather, combinations of 0.1 pM angiotensin II and PD 123319 (both 0.01 and 0.1 pM) enhanced S-I [3H]-noradrenaline efflux, whereas 0.1 pM angiotensin II alone was without effect. Moreover, losartan (0.1 pM) prevented the enhancement of S-I efflux by the combination of angiotensin II and PD 123319. 7 The present findings indicate that in the caudal artery of WKY and SH rats, and as previously found in Sprague-Dawley preparations, angiotensin II receptors similar to the ATIB subtype subserve enhancement of transmitter noradrenaline release. 8 As previously suggested for Sprague-Dawley caudal artery preparations, the synergistic prejunctional interaction of losartan and 0.1 pM angiotensin II in caudal artery preparations from WKY r...

show abstract

Section: Discussionmentioning

confidence: 98%

Angiotensin II receptors involved in the enhancement of noradrenergic transmission in the caudal artery of the spontaneously hypertensive rat

Cox

Story

Ziogas

1996

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…17 The effect of PD 123319 on Ang II-associated AA release by MSC deserves careful interpretation, since previous studies from this and other laboratories raised questions concerning the specificity of PD 123319 as a selective AT 2 -receptor antagonist. 45,46 We showed the existence of other forms of biologically active angiotensins 45 which may bind PD 123319. Our observation that Sar 1 -Thr 8 -Ang II mimics the individual effects of losartan and PD 123319 on MSC indicates that the effects of Ang II on AA release were mediated by an Ang II receptor mechanism, but this finding does not completely resolve the question of whether the responses elicited by PD 123319 were caused by blockade of AT 2 -receptors.…”

Section: Mcsf Secretion From Human Hs-5 Marrow Stromal Cells Stimulatmentioning

confidence: 97%

Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

Richmond

Tallant

Gallagher

et al. 2004

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

Introduction Angiotensin II (Ang II) is recognised as a regulator of haematopoiesis, but its actions within the bone marrow are not fully understood. Support of haematopoiesis by bone marrow stromal cells (MSC) is dependent on factors that include arachidonic acid and macrophage colony stimulating factor (MCSF), both of which are increased by Ang II stimulation in other tissues. To further elucidate the mechanisms of Ang II-regulated haematopoiesis, we determined whether Ang II-stimulation alters arachidonic acid release and MCSF secretion from MSC. Methods Cynomolgus monkey MSC isolated from bone marrow aspirates and the human HS-5 stromal cell line were studied for Ang II-mediated arachidonic acid (AA) release, while secretion of MCSF in response to Ang II was studied in HS-5 cells. Cells were labelled overnight with 3H-AA and the release of 3H-AA was measured in culture medium following 20 minutes stimulation with Ang II, alone or in combination with the AT1- or AT 2-receptor antagonists, losartan and PD 123319, respectively. MCSF secretion into culture medium was measured using an enzyme immunoassay following 24 hours of treatment with Ang II alone or in combination with losartan or PD 123319. Phorbol-myristate-acetate, known to stimulate release of AA and MCSF, was used as a positive control in both experiments. Results In response to Ang II, release of 3H-AA from monkey and human MSC was increased (p<0.05) to 147±4% and 124±3% of control, respectively. The AT1- and AT2-receptor antagonists, losartan and PD 123319, individually reduced Ang II-stimulated 3H-AA release. In contrast, Ang II had no effect on secretion of MCSF from HS-5 cells. Conclusions These results provide mechanistic evidence for Ang II-mediated haematopoiesis through AA release that may, in part, explain Ang II-facilitated recovery of haematopoiesis in experimental myelosuppression and the anaemias associated with Ang II receptor blockade.

show abstract

“…Systolic blood pressure and heart rate were measured once a week using the tail-cuff method. The ACE inhibitor enalapril, the AT 1 receptor antagonist losartan, or the AT 2 receptor antagonist PD123319 18 was then administered daily to SHR from 10 to 20 weeks of age. The dose of each drug was as follows: enalapril (30 mg ⅐ kg…”

Section: Animals and Experimental Protocolsmentioning

confidence: 99%

Interaction of mRNAs for Angiotensin II Type 1 and Type 2 Receptors to Vascular Remodeling in Spontaneously Hypertensive Rats

et al. 1998

View full text Add to dashboard Cite

Abstract-We administered angiotensin II (Ang II) receptor type 1 (AT 1 ) blockade (losartan, 40 mg ⅐ kg Ϫ1 ⅐ d Ϫ1), type II receptor (AT 2 ) blockade (PD123319, 100 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ), or angiotensin-converting enzyme (ACE) inhibitor (enalapril, 30 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. Control SHR and Wister-Kyoto rats (WKY) received a placebo for the same period. At the end of treatment, losartan and enalapril were both found to have significantly reduced the arterial systolic blood pressure and the collagen concentration to the level of WKY, whereas PD123319 had no effect. Enalapril and PD123319 significantly reduced the media cross-sectional area of the aorta in comparison to that of untreated SHR, which was still larger than that of the WKY; however, losartan did not change it. Using reverse transcription-polymerase chain reaction, we next examined the mRNA expressions for ACE, AT 1 receptor, and AT 2 receptor in experimental animals. We observed significantly enhanced mRNA expression for AT 1 and AT 2 receptors and ACE in untreated SHR compared with WKY. The AT 1 mRNA level was also significantly decreased in the SHR treated with either losartan or enalapril, whereas the AT 2 mRNA level was significantly decreased in the SHR treated with either PD123319 or enalapril in comparison to untreated SHR. The level of ACE mRNA was significantly decreased only in the SHR treated with enalapril. These results indicate that AT 1 receptor, but not AT 2 receptor, plays a crucial role in the remodeling of matrix tissue, while AT 2 receptor may play a role in the development of hypertrophy of smooth muscle in aorta in SHR, and that the reduction of hypertrophy of smooth muscle does not fully account for the suppression of hypertension. (Hypertension. 1998;32:467-472.) Key Words: angiotensin II Ⅲ receptors, angiotensin Ⅲ hypertrophy, vascular Ⅲ collagen Ⅲ rats, inbred SHR L ong-term hypertension is reported to be associated with cardiovascular remodeling, which consists of cardiovascular hypertrophy and an increase in the extracellular matrix (especially collagen).1,2 In spontaneously hypertensive rats (SHR), both left ventricular hypertrophy and the properties of characteristic vascular resistance are already present early in life, based on the results of a comparison with normotensive Wister-Kyoto rats (WKY).3,4 Angiotensin-converting enzyme (ACE) inhibitors can lower the blood pressure in SHR mainly by reducing the production of angiotensin II (Ang II).5 Ang II is considered to act as a growth-promoting factor in aortic smooth muscle cells, 6,7 while it also increases collagen synthesis in smooth muscle cells.8 ACE inhibitors suppress such vascular remodeling in experimental models, possibly through blood pressure-independent mechanisms. 9,10 Recently, a selective Ang II receptor antagonist has been developed that inhibits the renin-angiotensin system (RAS) more specifically than ACE inhibitors. Two main Ang II receptor subtypes, AT 1 and AT 2 , have been identified, a...

show abstract

Central administration of PD 123319 or EXP-3174 inhibits effects of angiotensin II

Cited by 23 publications

References 0 publications

Angiotensin II receptors involved in the enhancement of noradrenergic transmission in the caudal artery of the spontaneously hypertensive rat

Angiotensin II receptors involved in the enhancement of noradrenergic transmission in the caudal artery of the spontaneously hypertensive rat

Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

Interaction of mRNAs for Angiotensin II Type 1 and Type 2 Receptors to Vascular Remodeling in Spontaneously Hypertensive Rats

Contact Info

Product

Resources

About