Differential contractile responses and receptor properties of fetal systemic arteries and uterine arteries of pregnant sheep to angiotensin II: arteries with high proportions of AT2 receptors

Main Article Content

Julie Rae McMullen Eugenie Ruth Lumbers Karen Jane Gibson

Abstract

Uterine arteries from pregnant animals are one of only a few adult blood vessels which express predominantly AT2 receptors.  Fetal systemic arteries also contain a high density of AT2 receptors.  To assess whether fetal systemic arteries, like uterine arteries from pregnant animals, were relatively insensitive to angiotensin II (Ang II), we compared the contractile responses of fetal carotid arteries, as well as the receptor binding properties of fetal aortae, with those of uterine arteries from pregnant ewes.  Ang II receptor binding properties were measured in arterial membrane preparations using 125I [Sar1Ile8] Ang II.  Proportions of AT1 and AT2 receptors were determined by inhibiting 125I [Sar1Ile8] Ang II with losartan (AT1 antagonist) or PD 123319 (AT2 antagonist).  Both fetal aortae and uterine arteries contained predominantly AT2 receptors.  However, the AT2 receptor in fetal aortae had a higher affinity than that of the AT2 receptor in uterine arteries (P<0.05).  The contractile responses of fetal carotid arterial rings and uterine arterial rings to Ang II (4 µM) with and without antagonists were examined in vitro. Despite having similar proportions of Ang II receptor subtypes, fetal arterial rings were more responsive to Ang II in vitro than uterine arterial rings (P<0.05), possibly because of their greater density of AT1 receptors.  The recognised in vitro phenomenon of Ang II-induced tachyphylaxis was observed in uterine arterial rings but not fetal arterial rings. In addition, Ang II induced responses in fetal carotid rings were largely unaffected by losartan (1 mM) or PD 123319 (1 mM), whereas Ang II induced contractile responses of uterine arterial rings were inhibited by losartan (1 mM) and enhanced by PD 123319 (1 mM). Thus, it would appear that Ang II receptors in systemic arteries of fetal sheep may be functionally dissimilar to those in the uterine artery of pregnant sheep. 

Keywords: AT1 receptor, AT2 receptor, Ang II receptor antagonists

Article Details

How to Cite
MCMULLEN, Julie Rae; LUMBERS, Eugenie Ruth; GIBSON, Karen Jane. Differential contractile responses and receptor properties of fetal systemic arteries and uterine arteries of pregnant sheep to angiotensin II: arteries with high proportions of AT2 receptors. Medical Research Archives, [S.l.], v. 6, n. 5, may 2018. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1739>. Date accessed: 23 dec. 2024. doi: https://doi.org/10.18103/mra.v6i5.1739.
Section
Research Articles

References

1. Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, et al. Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 1995; 377(6551): 748-50.

2. Höhle S, Spitznagel H, Rascher W, Culman J, Unger T. Angiotensin AT1 receptor-mediated vasopressin release and drinking are potentiated by an AT2 receptor antagonist. Eur J Pharmacol 1995; 275(3): 277-82.

3. McMullen JR, Gibson KJ, Lumbers ER, Burrell JH, Wu J. Interactions between AT1 and AT2 receptors in uterine arteries from pregnant ewes. Eur J Pharmacol 1999; 378(2): 195-202.

4. Horiuchi M, Akishita M, Dzau VJ. Recent progress in the angiotensin II type 2 receptor research in the cardiovascular system. Hypertension 1999; 33(2): 613-21.

5. McCarthy CA, Widdop RE, Denton KM, Jones ES. Update of the angiotensin AT2 receptor. Curr Hypertens Rep. 2013; 15:25-30.

6. Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993; 45(2), 205-51.

7. Cox BE, Rosenfeld CR, Kalinyak JE, Magness RR, Shaul PW. Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy. Am J Physiol 1996; 271(1 Pt2): H212-21.

8. Cox BE, Word RA, Rosenfeld CR. Angiotensin II receptor characteristics and subtype expression in uterine arteries and myometrium during pregnancy. J Clin Endocrinol Metab 1996; 81(1): 49-58.

9. Burrell JH, Lumbers ER. Angiotensin receptor subtypes in the uterine artery during ovine pregnancy. Eur J Pharmacol 1997;330(2-3): 257-67.

10. Tsutsumi K, Strömberg C, Viswanathan M, Saavedra JM. Angiotensin-II receptor subtypes in fetal tissues of the rat: autoradiography, guanine nucleotide sensitivity, and association with phosphoinositide hydrolysis. Endocrinology 1991; 129(2): 1075-82.

11. Grady EF, Sechi LA, Griffin CA, Schambelan M, Kalinyak JE. Expression of AT2 receptors in the developing rat fetus. J Clin Invest 1991; 88(3): 921-33.

12. Kaiser JR, Cox BE, Roy TA, Rosenfeld CR. Differential development of umbilical and systemic arteries. I. Ang II receptor subtype expression. Am J Physiol 1998; 274(3 Pt2): R797-807.

13. Cox BE, Rosenfeld CR. Ontogeny of vascular angiotensin II receptor subtype expression in ovine development. Pediatr Res 1999; 45(3), 414-24.

14. Hegarty BD, Burrell JH, Gibson KJ, McMullen JR, Lumbers ER. Effect of cortisol on fetal ovine vascular angiotensin II receptors and contractility. Eur J Pharmacol 2000; 406(3): 439-48.

15. Burrell JH, Hegarty BD, McMullen JR. Lumbers ER. Effects of gestation on ovine fetal and maternal angiotensin receptor subtypes in the heart and major blood vessels. Exp Physiol 2001; 86(1): 71-82.

16. Cox BE, Liu XT, Fluharty SJ, Rosenfeld. Vessel-specific regulation of angiotensin II receptor subtypes during ovine development. Pediatr Res 2005; 57:124-132.

17. Davidson D, Eldemerdash A. Endothelium-derived relaxing factor: presence in pulmonary and systemic arteries of the newborn guinea pig. Pediatr Res 1990; 27(2): 128-32.

18. Greenwood FC, Hunter WM, Glover JS. The preparation of 131I-labelled human growth hormone of high specific radioactivity. Biochem J 1963; 89, 114-23.

19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.

20. McMullen JR, Gibson KJ, Lumbers ER, Burrell JH. Selective down-regulation of AT2 receptors in uterine arteries from pregnant ewes given 24-h intravenous infusions of angiotensin II. Regul Pept 2001; 99(2-3):119-29.

21. Motulsky H, Neubig R. Analyzing radioligand binding data. Curr Protoc Neurosci 2002; Chapter 7: Unit 7.5
22. McMullen JR, Gibson KJ, Lumbers ER, Burrell JH. 125I[Sar1Ile8] Angiotensin II has a different affinity for AT1 and AT2 receptor subtypes in ovine tissues. Regul Pept 2002; 105(2):83-92.

23. Arens Y, Chapados RA, Cox BE, Kamm KE, Rosenfeld CR. Differential development of umbilical and systemic arteries. II. Contractile proteins. Am J Physiol 1998; 274(6 Pt2): R1815-23.

24. Segar JL, Barna TJ, Acarregui MJ, Lamb FS. Responses of fetal ovine systemic and umbilical arteries to angiotensin II. Pediatr Res 2001; 49:823-33.

25. Stevenson KM, Gibson KJ, Lumbers ER. Effects of losartan on the cardiovascular system, renal haemodynamics and function and lung liquid flow in fetal sheep. Clin Exp Pharmacol Physiol 1996; 23(2): 125-33.

26. Miura S, Feng Y, Husain A, Karnik SS. Role of aromaticity of agonist switches of angiotensin II in the activation of the AT1 receptor. J Biol Chem 1999; 274(11):7103-10.

27. Sim MK, Kuttan SC. Effects of noradrenaline and prostaglandin F2a on angiotensin-induced contraction and tachyphylaxis in rat aortic rings. Pharmacol Toxicol 1992; 70(1): 60-4.

28. Kuttan SC, Sim MK. Angiotensin II-induced tachyphylaxis in aortas of normo- and hypertensive rats: changes in receptor affinity. Eur J Pharmacol 1993; 232:173-180.

29. Gruetter CA, Ryan ET, Schoepp DD. Endothelium enhances tachyphylaxis to angiotensins II and III in rat aorta. Eur J Pharmacol 1987; 143:139-142.

30. Thomas WG. Regulation of angiotensin II type 1 (AT1) receptor function. Regul Pept 1999; 79(1): 9-23.

31. Oliveira L, Costa-Neto CM, Nakaie CR, Schreier S, Shimuta SI, Paiva ACM. The angiotensin II AT1 receptor structure-activity correlations in the light of rhodopsin structure. Physiol Rev 2007; 87: 565-92.

32. Alves FL, Oliveira VX, Miranda A. Angiotensin II analogues with N-terminal lactam bridge cyclization: an overview of AT1 receptor activation and tachyphylaxis. Chem Biol Drug Des 2016; 88: 677-82.

33. Linder AE, Thakali KM, Thompson JM, Watts SW, Webb RC, Leite R. Methyl--cyclodextrin prevents angiotensin II-induced tachyphylactic contractile responses in rat aorta. J Pharmacol Exp Ther 2007; 323(1):78-84.
34. Hein L. Meinel L, Pratt RE, Dzau VJ, Kobilka BK. Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: Evidence for selective sorting of receptor and ligand. Mol. Endocrinol. 1997; 11(9): 1266-77.

35. Li Q, Zhang J, Pfaffendorf M, van Zwieten PA. Comparative effects of angiotensin II and its degradation products angiotensin III and angiotensin IV in rat aorta. Brit J Pharmacol 1995; 116:2963-70.

36. Tsutsumi K, Saavedra JM. Heterogeneity of angiotensin II AT2 receptors in the rat brain. Mol Pharmacol 1992; 41:290-297.

37. Speth RC. [125I]CGP 42112 binding reveals differences between rat brain and adrenal AT2 receptor binding sites. Regul Pept 1993; 44(2): 189-97.

38. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T. International Union of Pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev 2000; 52:415-72.