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. 1994 May;112(1):200–206. doi: 10.1111/j.1476-5381.1994.tb13052.x

Attenuated renal response to moxonidine and rilmenidine in one kidney-one clip hypertensive rats.

P Li 1, S B Penner 1, D D Smyth 1
PMCID: PMC1910300  PMID: 8032642

Abstract

1. I1 non-adrenoceptor, imidazoline receptor agonists, such as moxonidine, increase urine flow rate and sodium excretion following infusion into the renal artery. The functions of these agonists in genetic and acquired models of hypertension have not been determined. 2. We therefore studied the renal effects of two known non-adrenoceptor, imidazoline receptor agonists, rilmenidine and moxonidine, in 1K-1C hypertensive and 1K-sham normotensive rats. Rilmenidine (0, 3, 10, 30 nmol kg-1 min-1) or moxonidine (0, 1, 3, 10 nmol kg-1 min-1) was infused directly into the renal artery (30 gauge needle) of 1K-sham normotensive and 1K-1C hypertensive rats. 3. In 1K-sham normotensive rats, rilmenidine and moxonidine produced dose related increases in urine flow rate, sodium excretion and osmolar clearance. Both rilmenidine and moxonidine failed to increase urine flow rate, sodium excretion and osmolar clearance in 1K-1C hypertensive rats to the same extent as in 1K-sham animals. At comparable doses, rilmenidine had no effect, while moxonidine (3 and 10 nmol kg-1 min-1) did result in a small increase in urine volume and osmolar clearance which was less than that observed in the 1K sham control animals. 4. These studies indicate that the renal effects of non-adrenoceptor, imidazoline receptor stimulation are diminished in 1K-1C hypertensive rats compared with 1K-sham normotensive rats. Whether this decrease in activity of the natriuretic non-adrenoceptor, imidazoline receptors contributes to the increase in blood pressure in the 1K-1C acquired model of hypertension remains to be determined.

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Selected References

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  1. Allan D. R., Penner S. B., Smyth D. D. Renal imidazoline preferring sites and solute excretion in the rat. Br J Pharmacol. 1993 Apr;108(4):870–875. doi: 10.1111/j.1476-5381.1993.tb13480.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atlas D. Clonidine-displacing substance (CDS) and its putative imidazoline receptor. New leads for further divergence of alpha 2-adrenergic receptor activity. Biochem Pharmacol. 1991 Jun 1;41(11):1541–1549. doi: 10.1016/0006-2952(91)90152-u. [DOI] [PubMed] [Google Scholar]
  3. Blandford D. E., Smyth D. D. Dose selective dissociation of water and solute excretion after renal alpha-2 adrenoceptor stimulation. J Pharmacol Exp Ther. 1988 Dec;247(3):1181–1186. [PubMed] [Google Scholar]
  4. Blandford D. E., Smyth D. D. Role of vasopressin in response to intrarenal infusions of alpha-2 adrenoceptor agonists. J Pharmacol Exp Ther. 1990 Oct;255(1):264–270. [PubMed] [Google Scholar]
  5. Boyajian C. L., Loughlin S. E., Leslie F. M. Anatomical evidence for alpha-2 adrenoceptor heterogeneity: differential autoradiographic distributions of [3H]rauwolscine and [3H]idazoxan in rat brain. J Pharmacol Exp Ther. 1987 Jun;241(3):1079–1091. [PubMed] [Google Scholar]
  6. Bricca G., Dontenwill M., Molines A., Feldman J., Belcourt A., Bousquet P. The imidazoline preferring receptor: binding studies in bovine, rat and human brainstem. Eur J Pharmacol. 1989 Mar 14;162(1):1–9. doi: 10.1016/0014-2999(89)90597-9. [DOI] [PubMed] [Google Scholar]
  7. Coupry I., Podevin R. A., Dausse J. P., Parini A. Evidence for imidazoline binding sites in basolateral membranes from rabbit kidney. Biochem Biophys Res Commun. 1987 Sep 30;147(3):1055–1060. doi: 10.1016/s0006-291x(87)80177-8. [DOI] [PubMed] [Google Scholar]
  8. Ernsberger P., Damon T. H., Graff L. M., Schäfer S. G., Christen M. O. Moxonidine, a centrally acting antihypertensive agent, is a selective ligand for I1-imidazoline sites. J Pharmacol Exp Ther. 1993 Jan;264(1):172–182. [PubMed] [Google Scholar]
  9. Ernsberger P., Giuliano R., Willette R. N., Reis D. J. Role of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medulla. J Pharmacol Exp Ther. 1990 Apr;253(1):408–418. [PubMed] [Google Scholar]
  10. Feldman J., Tibiriça E., Bricca G., Dontenwill M., Belcourt A., Bousquet P. Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit. Br J Pharmacol. 1990 Jul;100(3):600–604. doi: 10.1111/j.1476-5381.1990.tb15853.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fukuda K., Kuchii M., Hano T., Mohara O., Miyamoto Y., Nishio I., Masuyama Y. Changes in renal alpha 2-adrenoceptor in experimental hypertension in rats. Jpn Circ J. 1983 Oct;47(10):1221–1226. doi: 10.1253/jcj.47.1221. [DOI] [PubMed] [Google Scholar]
  12. Gomez R. E., Ernsberger P., Feinland G., Reis D. J. Rilmenidine lowers arterial pressure via imidazole receptors in brainstem C1 area. Eur J Pharmacol. 1991 Mar 26;195(2):181–191. doi: 10.1016/0014-2999(91)90534-w. [DOI] [PubMed] [Google Scholar]
  13. Li P., Smyth D. D. Decreased renal activity of vasopressin in spontaneously hypertensive rats. J Hypertens. 1993 Jan;11(1):41–48. doi: 10.1097/00004872-199301000-00007. [DOI] [PubMed] [Google Scholar]
  14. Michel M. C., Brodde O. E., Insel P. A. Peripheral adrenergic receptors in hypertension. Hypertension. 1990 Aug;16(2):107–120. doi: 10.1161/01.hyp.16.2.107. [DOI] [PubMed] [Google Scholar]
  15. Michel M. C., Brodde O. E., Schnepel B., Behrendt J., Tschada R., Motulsky H. J., Insel P. A. [3H]idazoxan and some other alpha 2-adrenergic drugs also bind with high affinity to a nonadrenergic site. Mol Pharmacol. 1989 Mar;35(3):324–330. [PubMed] [Google Scholar]
  16. Michel M. C., Kanczik R., Khamssi M., Knorr A., Siegl H., Beckeringh J. J., Brodde O. E. Alpha and beta-adrenoceptors in hypertension. I. Cardiac and renal alpha 1-, beta 1-, and beta 2-adrenoceptors in rat models of acquired hypertension. J Cardiovasc Pharmacol. 1989 Mar;13(3):421–431. doi: 10.1097/00005344-198903000-00010. [DOI] [PubMed] [Google Scholar]
  17. Michel M. C., Regan J. W., Gerhardt M. A., Neubig R. R., Insel P. A., Motulsky H. J. Nonadrenergic [3H]idazoxan binding sites are physically distinct from alpha 2-adrenergic receptors. Mol Pharmacol. 1990 Jan;37(1):65–68. [PubMed] [Google Scholar]
  18. Olmos G., Miralles A., Barturen F., Garcia-Sevilla J. A. Characterization of brain imidazoline receptors in normotensive and hypertensive rats: differential regulation by chronic imidazoline drug treatment. J Pharmacol Exp Ther. 1992 Mar;260(3):1000–1007. [PubMed] [Google Scholar]
  19. Regunathan S., Meeley M. P., Reis D. J. Clonidine-displacing substance from bovine brain binds to imidazoline receptors and releases catecholamines in adrenal chromaffin cells. Mol Pharmacol. 1991 Dec;40(6):884–888. [PubMed] [Google Scholar]
  20. Sáiz J., Lara B., Torres A., Sánchez A. Hypertensinogenic factors and renal alpha-adrenoceptors in young SHR and WKY rats. Life Sci. 1987 Nov 16;41(20):2261–2268. doi: 10.1016/0024-3205(87)90537-6. [DOI] [PubMed] [Google Scholar]
  21. Sánchez A., Torres A., Sáiz J. Renal alpha-adrenoceptor density and blood pressure in SHR rats exposed chronically to prazosin and/or yohimbine. Clin Exp Hypertens A. 1989;11(1):119–136. doi: 10.3109/10641968909035295. [DOI] [PubMed] [Google Scholar]
  22. Wilson S. K. Peripheral alpha-1 and alpha-2 adrenergic receptors in three models of hypertension in rats: an in vitro autoradiography study. J Pharmacol Exp Ther. 1991 Feb;256(2):801–810. [PubMed] [Google Scholar]
  23. Wong L. T., Smyth D. D., Sitar D. S. Interference with renal organic cation transport by (-)- and (+)-nicotine at concentrations documented in plasma of habitual tobacco smokers. J Pharmacol Exp Ther. 1992 Apr;261(1):21–25. [PubMed] [Google Scholar]
  24. Yamada S., Yamamura H. I., Roeske W. R. Alterations in central and peripheral adrenergic receptors in deoxycorticosterone/salt hypertensive rats. Life Sci. 1980 Dec 15;27(24):2405–2416. doi: 10.1016/0024-3205(80)90512-3. [DOI] [PubMed] [Google Scholar]

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