Share This Article:

Differential Effects of Angiotensin II on Intra-Renal Hemodynamics in Rats; Contribution of Prostanoids, NO and K+ Channels

Abstract Full-Text HTML Download Download as PDF (Size:853KB) PP. 388-396
DOI: 10.4236/pp.2012.34052    2,488 Downloads   4,820 Views   Citations

ABSTRACT

Many agents are known to cause qualitative and quantitative differences in intrarenal blood flow. This study tested the hypothesis that angiotensin II (AII) evokes a differential effect on cortical (CBF) and medullary blood flow (MBF) and that AT2 receptor mediates AII-induced increase in renal MBF by mechanisms related to nitric oxide (NO) and prostanoids. AII (100, 300 and 1000 ng/kg/min) increased mean arterial blood pressure (MABP) by 24% ± 7% (p < 0.05); decreased CBF by 30% ± 2% (p < 0.05); but increased MBF by 21% ± 8% (p < 0.05). Indomethacin (5 mg/kg), enhanced AII effects on MABP by 154% ± 26% (p < 0.05), MBF by 141% ± 46 % but decreased CBF by 74% ± 54% (p < 0.05) indicating the involvement of dilator prostanoids in the systemic and medullary circulation but constrictor prostanoids in the cortex. NG nitro-L-arginine (L-NNA), an inhibitor of NO synthase (100 mg/L in drinking water) enhanced AII effects on MABP (169 ± 75, p < 0.05) and decreased CBF (107% ± 50%, p < 0.05) but blunted the effects of AII on MBF (150% ± 21%, p < 0.05). 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 2 mg/kg), a guanylyl cyclase inhibitor, enhanced AII effects on MABP (118% ± 32% , p < 0.05) and decreased CBF(85% ± 47% , p < 0.05) but blunted the effects of AII on MBF (96% ± 15%, p < 0.05). However, glibenclamide (20 μg/kg), a KATP channel blocker, did not affect intra-renal hemodynamics elicited by AII. Blockade of AT2 receptors with PD123319 (50 μg/kg/min) did not change basal or AII-induced changes MABP or CBF but blunted AII-induced increase in MBF by 60% ± 11 % (p < 0.05). CGP42112 (10 μg/kg/min), an AT2 receptor agonist, elicited a reduction in MABP and increases in CBF and MBF that were abolished or attenuated by PD123319. These findings demonstrate that AII elicited differential changes in intrarenal blood flow; an AT1-mediated reduction in CBF but an AT2-mediated increase in MBF. The AT2 receptor-mediated increase in MBF involves guanylase cyclase, NO and dilator prostanoids but not KATP channels.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

I. Igbe, E. Omogbai and A. Oyekan, "Differential Effects of Angiotensin II on Intra-Renal Hemodynamics in Rats; Contribution of Prostanoids, NO and K+ Channels," Pharmacology & Pharmacy, Vol. 3 No. 4, 2012, pp. 388-396. doi: 10.4236/pp.2012.34052.

References

[1] B. Badzyńska, M. Grzelec-Mojzesowicz, L. Dobrowolski, and J. Sadowski, “Differential effect of angiotensin II on blood circulation in the renal medulla and cortex of anaesthetised rats” Journal of Physiology, Vol. 538, No.1, 2002, pp. 159–166.
[2] A.W. Cowley, “Role of the renal medulla in volume and arterial blood pressure regulation” American Journal of Physiology, Vol. 273, 1997, pp. R1–R15
[3] R.M. Carey, “Update on the role of the AT2 receptor” Current Opinion in Nephrology and Hypertension, Vol. 14, 2005, pp. 67–71
[4] W.A. Cupples, T. Sakai, and D.J. Marsh DJ “Angiotensin II and prostaglandins in control of vasa recta blood flow”. American Journal of Physiology, Vol. 254, 1988, pp. F417–F424
[5] R.G. Evans, A.C. Madden and K.M. Denton, “Diversity of responses of renal cortical and medullary blood flow to vasoconstrictors in conscious rabbits” Acta Physiology Scandinavia, Vol. 169, 2000, pp. 297–308.
[6] L.L. Walker, A.A. Rajaratne, J.R. Blair-West and P.J. Harris, “The effects of angiotensin II on blood perfusion in the rat renal papilla” Journal of Physiology Vol. 519, 1999, pp. 273–278.
[7] D.L. Mattson, H. Raff, and R.J. Roman, “Influence of angiotensin II on pressure natriuresis and renal hemodynamics in volume expanded rats” American Journal of Physiology Regul Integr Comp Physiol Vol. 260, 1991, pp. R1200–R1209.
[8] C.L. Huang, G. Davis and E.J. Johns, “A study of the action of angiotensin II on perfusion through the cortex and papilla of the rat kidney” Experimental Physiology Vol. 76, 1991, pp. 787–798.
[9] T.L. Pallone, C.R. Robertson and R.L. Jamison, “Renal medullary microcirculation” Physiol Rev, Vol. 70, 1990, pp. 885–920.
[10] S. Lu, D.L. Mattson, R.J. Roman, C.G. Becker, and A.W. Cowley Jr. “Assessment of changes in intra-renal blood flow in conscious rats using laser-Doppler flowmetry” American J ournal of Physiology Renal Fluid Electrolyte Physiology Vol. 264, 1993, pp. F956–F962
[11] M.S. Nobes, P.J. Harris, H. Yamada, and F.A.O. Mendelsohn, “Effects of angiotensin on renal cortical and papillary blood flows measured by laser-Doppler flowmetry” American J ournal of Physiology Renal Fluid Electrolyte Physiology, Vol. 261, 1991, pp. F998–F1006
[12] N.W. Rajapakse, J.J. Oliver and R.G. Evans, “Nitric oxide in responses of regional kidney blood flow to vasoactive agents in anesthetized rabbits” Journal of Cardi-ovascular Pharmacology, Vol.40, 2002, pp. 210–219.
[13] J.J Oliver, N.W. Rajapakse and R.G. Evans, “Effects of indomethacin on responses of regional kidney perfusion to vasoactive agents in rabbits” Clinical Experimental Pharmacology and Physiology, Vol. 29, 2002, pp. 873–879.
[14] A.P. Zou, F. Wu, A.W and Cowley Jr., “Protective effect of angiotensin II–induced increase in nitric oxide in the renal medullary circulation” Hypertension, Vol. 31, 1998, pp. 271–276.
[15] A.O. Oyekan, “Contributions of Nitric Oxide and Prostanoids and Their Signaling Pathways to the Renal Medullary Vasodilator Effect of U46619 (9-11-Dideoxy-11α, 9a-Epoxymethano-Prostaglandin F2a) in the Rat” Journal of Pharmacology and Experimental Therapeutics, Vol. 304, 2003, pp. 507–512
[16] J.L. Williams, D. Cartland, A. Hussain and S. Egginton, “A differential role for nitric oxide in two forms of physiological angiogenesis in mouse” Journal of Physiology Vol. 570, No.3, 2006, pp. 445–454
[17] S. Crestani, Y.D. Rattmann, T.R. Cipriani, L.M. de Souza, M. Iacomini, C.A. Kassuya, M.C. Marques and J.E. da Silva-Santos, “A potent and nitric oxide-dependent hypotensive effect induced in rats by semi-purified fractions from Maytenus ilicifolia” Vascular Pharmacology. Vol. 51, No.1, 2009, pp. 57-63
[18] H.C.D. Souza, H.C. Salgado, G. Ballejo and M.C.O. Salgado, “SR141716A-Sensitive Enhancement of ET-1 Hypotensive Effect by Chronic NOS Inhibition” Hypertension Vol. 42, No. 2, 2003, pp. 802-805.
[19] L.M. Duke, G.A Eppel, R.E. Widdop and R.G. Evans, “Disparate Roles of AT2 Receptors in the Renal Cortical and Medullary Circulations of Anesthetized Rabbits” Hypertension Vol. 42, 2003, pp. 200-205
[20] S.Y. Chou, J.G. Porush and P.F. Faubert, “Renal medullary circulation: Hormonal control” Kidney International Vol. 37, 1990, pp. 1-13.
[21] D.S.A. Majid, M. Godfrey and L.G. Navar, “Pressure natriuresis and renal medullary blood flow in dogs” Hypertension Vol. 29, 1997, pp. 1051-1057.
[22] S.A. Omoro, D.S.A. Majid, S.S. El-Dahr and L.G. Navar (1999) “Kinin influences on renal regional blood flow responses to angiotensin-converting enzyme inhibition in dogs” American Journal of Physiology Renal Physiology, Vol. 276, 1999, pp. F271-F277
[23] N. Parekh, L. Dobrowolski, A.P. Zou and M. Steinhausen, “Nitric oxide modulates angiotensin II- and nore-pinephrine-dependent vasoconstriction in rat kidney” American Journal of Physiology Regulatory Intergrative and Comparative Physiology, Vol. 270, 1996, pp. R630-R635
[24] R.G. Evans, G. Bergstroèm and A.J. Lawrence, “Effects of the vasopressin V1 agonist [Phe2,Ile3,Orn8]-vasopressin on regional kidney perfusion and renal excretory function in anesthetized rabbits” Journal of Cardiovascular Pharmacology Vol. 32, 1998a, pp. 571-581
[25] L.G. Navar, B.L. Harrison, J.D. Imig, et al. “Role of AT1 receptor in target organ disease : A functional perspective” American Journal of Hypertension, Vol. 13, 2000, pp. 45S–54S
[26] R.G. Evans, G.A. Head, G.A. Eppel, S.L. Burke and N.W. Rajapakse “Frontiers in Research Series:Neural, Hormonal and Renal Interactions in Long-term Blood Pressure Control II: Angiotensin II and neurohumoral control of the renal medullary Circulation” Clinical and Experimental Pharmacology and Physiology Vol.37, 2010, pp. 58–69
[27] P.A. Ortiz, N.J. Hong, D. Wang and J.L. Garvin “Gene transfer of eNOS to the thick ascending limb of eNOS-KO mice restores the effects of L-arginine on NaCl absorption” Hypertension Vol. 42, 2003, pp. 674–679
[28] H.M. Siragy and R.M. Carey “The subtype-2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3,5-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats” Journal of Clinical Investigation. Vol. 97, 1996, pp. 1978–1982
[29] M.D. Breyer and R.M. Breyer “Prostanglandin E receptors and the kidney” American Journal of Physiology, Renal Physiology Vol.279, 2000, no. 1. pp F12-F23
[30] A. Yared, V. Kon and I. Ichikawa “Mechanism of preservation of glomerular perfusion and filtration during acute extracellular volume depletion: importance of intrarenal vasopressin prostaglandin interaction for protecting kidneys from constrictor action of vasopressin” Journal of Clinical Investigation Vol.75, 1985, pp. 1477–1487
[31] F.G. Knox and J.P. Granger, “Control of sodium excretion: An integrative approach” In: Windhager EE, editor. Renal Physiology. New York and Oxford: Oxford University Press; 1992, pp. 944–945.
[32] J. Sadowski, E. Kompanowska-Jezierska, L. Dobrowolski, A. Walkowska and B. Badzynska (1997) “Simultaneous recording of tissue ion content and blood flow in rat renal medulla: Evidence on interdependence” American Journal of Physiology Renal Physiology. Vol. 273, 1997, pp. F658–F662
[33] E. Kompanowska-Jezierska, A. Walkowska and J. Sadowski “Exaggerated volume expansion natriuresis in rats preloaded with hypertonic saline: A paradoxical enhancement by inhibition of prostaglandin synthesis” Acta Physiologica Scandinavica. Vol. 167, 1999, pp.189–194.
[34] H.G. Klieber and J. Daut, “A glibenclamide-sensitive potassium conductance in terminal arterioles isolated from guinea pig heart” Cardiovascular Research Vol. 28, 1994, pp. 823–830.
[35] S.M. Gardiner, P.A. Kemp, J.E. March, B. Fallgren and T. Bennett, “Effects of glibenclamide on the regional haemodynamic actions of α-trinositol and its influence on responses to vasodilators in conscious rats” British Journal of Pharmacology Vol. 117, 1996, pp. 507–515
[36] A.L. Salzman, A. Vromen, A. Denenberg and C. Szabo “KATP-channel inhibition improves hemodynamics and cellular energetics in hemorrhagic shock” American Journal of Physiology Heart Circulation Physiology Vol. 272, 1997, pp. H688–694
[37] T. Mimuro, T. Kawata, T. Onuki, S. Hashimoto, K. Tsuchiya, H. Nihei and T. Koike, “The attenuated effect of ATP-sensitive K+ channel opener pinacidil on renal haemodynamics in spontaneously hypertensive rats” European Journal of Pharmacology Vol. 358, 1998, pp. 153–160
[38] C. Cao, W. Lee-Kwon, E.P. Silldorff and T.L. Pallone, “KATP-channel conductance of descending vasa recta pericytes” American Journal of Physiology Renal Physiology Vol. 289, 2005, pp. F1235–F1245.
[39] M. DeGasparo, K.J. Catt and T. Inagami, “International Union of Pharmacology XXIII. The angiotensin II receptors” Pharmacology Review Vol.52, 2000, pp. 415–472.
[40] H. Matsubara, T. Sugaya, S. Murasawa, Y. Nozawa, Y. Mori and H. Masaki “Tissue-specific expression of human angiotensin II AT1 and AT2 receptors and cellular localization of subtype mRNAs in adult human renal cortex using in situ hybridization” Nephron Vol. 80, 1998, pp. 25-34.
[41] L.M. Duke, R.E. Widdop, M.M. Kett and R.G. Evans “AT2 receptors mediate tonic renal medullary vasocon-striction in renovascular hypertension” British Journal of Pharmacology Vol.144, 2005, pp. 486–492
[42] R.E. Widdop, E.S. Jones, R.E. Hannan and T.A. Gaspari (2003). “Angiotensin AT2 receptors: cardiovascular hope or hype?” British Journal of Pharmacology, Vol. 140, 2003, pp. 809?824.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.