New roles with implications in nephro-protection and blood pressure regulation
Abstract
Renal dopamine (DA) regulates water and sodium excretion and, doing so, controls blood pressure. Renal epithelial cells produce DA by decarboxylation of filtered l-dopa and inactivate DA by monoamineoxidase (MAO) and catechol-O-methyl transferase (COMT). Dopamine interacts with specific receptors (D1R and D2R). The aim of this work is to study urinary DA excretion (UDA*V) and MAO and COMT activities in rats under different sodium intake. Four groups according to Na+ intake and treatment were studied: Normal (NS, NaCl 0.24%), Low (BS, 0.02%) and High sodium (HS, 1%) for 5 days. In group four, NS, BS and HS rats received SCH 23390 (1 mg/kg SC), D1R antagonist, the last three days. Results: UDA*V (ng/d/100g bwt) was lower in BS 571±30 vs NS 730±45, p< 0.01 and was increased in HS to 1443±203 p<0.01vs NS and p<0.001 vs BS. In BS rats MAO activity (nmol/mg/h) increased in renal cortex to 9.44±0.55 vs NS 7.66±0.52, p<0.05, while MAO decreased in HS cortex to 6.3±0.25, p<0.05 vs NS. COMT activity (pmol/mg/h), increased in cortex of BS rats to 15.67±1.23 vs 11.04±0.13 in NS group, p<0.05. Regardless Na+ intake, MAO was always higher in cortex than in renal medulla, while COMT did not show differences between cortex and medulla. SCH 23390 markedly decreased diuresis and natriuresis in HS rats and Na+ excretion in NS and increased systolic pressure in BS. Conclusion: dopamine and Na+ excretion are positively related to Na+ intake. MAO and COMT are involved in this response mainly mediated by D1R stimulation.
References
De Luca Sarobe V, Di Ciano L, Carranza MA, Levin GM, Arrizurieta E, Ibarra FR. Actividad del sistema dopaminérgico renal en ratas con distinto contenido de sodio en la dieta. Rev Nefrol Dial Traspl. 2010;30(4):153-60.
Carranza A, Nowicki S, Barontini M, Armando I. L-Dopa uptake and dopamine production in proximal tubular cells are regulated by beta(2)-adrenergic receptors. Am J Physiol Renal Physiol. 2000;279(1):F77-83.
Ibarra FR, Aguirre J, Nowicki S, Barontini M, Arrizurieta EE, Armando I. Demethylation of 3-O-methyldopa in the kidney: a possible source for dopamine in urine. Am J Physiol. 1996;270(5 Pt 2):F862-8.
Ibarra FR, Armando I, Nowicki S, Carranza A, De Luca Sarobe V, Arrizurieta EE, et al. Dopamine is metabolised by different enzymes along the rat nephron. Pflugers Arch. 2005;450(3):185-91.
Aperia AC. Intrarenal dopamine: a key signal in the interactive regulation of sodium metabolism. Annu Rev Physiol. 2000;62:621-47.
Honda K, Nunokawa T, Matsuzaki K, Nagasaka M. Dopamine tonically modulates natriuresis in the saline-expanded dogs. Hypertens Res. 1995;18(Suppl 1):S147-50.
Felder CC, McKelvey AM, Gitler MS, Eisner GM, Jose PA. Dopamine receptor subtypes in renal brush border and basolateral membranes. Kidney Int. 1989;36:183-93.
Zeng C, Armando I, Luo Y, Eisner GM, Felder RA, Jose PA. Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice. Am J Physiol Heart Circ Physiol. 2008;294(2):H551-69.
Ozono R, Ueda A, Oishi Y, Yano A, Kambe M, Katsuki M, et al. Dopamine D2 receptor modulates sodium handling via local production of dopamine in the kidney. J Cardiovasc Pharmacol. 2003;42 Suppl 1:S75-9.
Choi MR, Lee BM, Medici C, Correa AH, Fernandez BE. Effects of angiotensin II on renal dopamine metabolism: synthesis, release, catabolism and turnover. Nephron Physiol. 2010;115(1):1-7.
De Luca Sarobe V, Nowicki S, Carranza A, Levin G, Barontini M, Arrizurieta E, et al. Low sodium intake induces an increase in renal monoamine oxidase activity in the rat. Involvement of an angiotensin II dependent mechanism. Acta Physiol Scand. 2005;185(2):161-7.
Khan F, Spicarová Z, Zelenin S, Holtbäck U, Scott L, Aperia A. Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells. Am J Physiol Renal Physiol. 2008;295(4):F1110-6.
Jordan BA, Devi LA. G-protein-coupled receptor heterodimerization modulates receptor function. Nature. 1999;399(6737):697-700.
Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, et al. Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. J Clin Invest. 2011;121(7):2845-54.
Yang S, Yao B, Zhou Y, Yin H, Zhang MZ, Harris RC. Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury. Am J Physiol Renal Physiol. 2012;302(6):F742-9.
Li D, Scott L, Crambert S, Zelenin S, Eklöf AC, Di Ciano L, et al. Binding of losartan to angiotensin AT1 receptors increases dopamine D1 receptor activation. J Am Soc Nephrol. 2012;23(3):421-8.