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Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature.
Eur J Pharmacol. 2017 Sep 15; 811:38-47.EJ

Abstract

Accumulating evidence from clinical and experimental studies indicates that the incretin glucagon-like peptide-1 (GLP-1) elicits blood-pressure lowering effects via its diuretic, natriuretic and vasodilatory properties. The present study investigated whether acute infusion of GLP-1 induces diuresis and natriuresis in spontaneously hypertensive rats (SHRs). Additionally, we examined whether GLP-1 influences the vascular reactivity of the renal arteries of normotensive and hypertensive rats and elucidated the underlying mechanisms. We found that the increase in urinary output and urinary sodium excretion in response to systemic infusion of GLP-1 for 30min in SHRs was much less pronounced than in normotensive rats. The diuretic and natriuretic actions of GLP-1 in normotensive rats were accompanied by increases in GFR and RBF and a reduction in RVR through activation of the cAMP signaling pathway. However, no changes in renal hemodynamics were observed in SHRs. Similarly, GLP-1 induced an endothelium-independent relaxation effect in the renal arteries of normotensive rats, whereas the renal vasculature of SHRs was unresponsive to this vasodilator. The absence of a GLP-1-induced renal artery vasodilator effect in SHRs was associated with lower expression of the GLP-1 receptor, blunted GLP-1-induced increases in cAMP production and higher activity and expression of the GLP-1 inactivating enzyme dipeptidyl peptidase IV relative to the renal arteries of normotensive rats. Collectively, these results demonstrate that the renal acute responses to GLP-1 are attenuated in SHRs. Thus, chronic treatment with incretin-based agents may rely upon the upregulation of GLP-1/GLP-1 receptor signaling in the kidneys of hypertensive patients and experimental models.

Authors+Show Affiliations

Heart Institute (InCor), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.Heart Institute (InCor), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.Heart Institute (InCor), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.Heart Institute (InCor), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.Department of Nephrology (LIM-12), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.Department of Nephrology (LIM-12), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.Heart Institute (InCor), University of São Paulo Medical School, São Paulo, São Paulo, Brazil. Electronic address: adriana.girardi@incor.usp.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28576404

Citation

Savignano, Fernanda A., et al. "Attenuated Diuresis and Natriuresis in Response to Glucagon-like Peptide-1 in Hypertensive Rats Are Associated With Lower Expression of the Glucagon-like Peptide-1 Receptor in the Renal Vasculature." European Journal of Pharmacology, vol. 811, 2017, pp. 38-47.
Savignano FA, Crajoinas RO, Pacheco BPM, et al. Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature. Eur J Pharmacol. 2017;811:38-47.
Savignano, F. A., Crajoinas, R. O., Pacheco, B. P. M., Campos, L. C. G., Shimizu, M. H. M., Seguro, A. C., & Girardi, A. C. C. (2017). Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature. European Journal of Pharmacology, 811, 38-47. https://doi.org/10.1016/j.ejphar.2017.05.054
Savignano FA, et al. Attenuated Diuresis and Natriuresis in Response to Glucagon-like Peptide-1 in Hypertensive Rats Are Associated With Lower Expression of the Glucagon-like Peptide-1 Receptor in the Renal Vasculature. Eur J Pharmacol. 2017 Sep 15;811:38-47. PubMed PMID: 28576404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature. AU - Savignano,Fernanda A, AU - Crajoinas,Renato O, AU - Pacheco,Bruna P M, AU - Campos,Luciene C G, AU - Shimizu,Maria Heloisa M, AU - Seguro,Antonio Carlos, AU - Girardi,Adriana C C, Y1 - 2017/05/30/ PY - 2017/05/15/received PY - 2017/05/25/revised PY - 2017/05/29/accepted PY - 2017/6/4/pubmed PY - 2018/5/31/medline PY - 2017/6/4/entrez KW - Hypertension KW - Incretin KW - Renal artery KW - Renal function KW - Renal vascular resistance SP - 38 EP - 47 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 811 N2 - Accumulating evidence from clinical and experimental studies indicates that the incretin glucagon-like peptide-1 (GLP-1) elicits blood-pressure lowering effects via its diuretic, natriuretic and vasodilatory properties. The present study investigated whether acute infusion of GLP-1 induces diuresis and natriuresis in spontaneously hypertensive rats (SHRs). Additionally, we examined whether GLP-1 influences the vascular reactivity of the renal arteries of normotensive and hypertensive rats and elucidated the underlying mechanisms. We found that the increase in urinary output and urinary sodium excretion in response to systemic infusion of GLP-1 for 30min in SHRs was much less pronounced than in normotensive rats. The diuretic and natriuretic actions of GLP-1 in normotensive rats were accompanied by increases in GFR and RBF and a reduction in RVR through activation of the cAMP signaling pathway. However, no changes in renal hemodynamics were observed in SHRs. Similarly, GLP-1 induced an endothelium-independent relaxation effect in the renal arteries of normotensive rats, whereas the renal vasculature of SHRs was unresponsive to this vasodilator. The absence of a GLP-1-induced renal artery vasodilator effect in SHRs was associated with lower expression of the GLP-1 receptor, blunted GLP-1-induced increases in cAMP production and higher activity and expression of the GLP-1 inactivating enzyme dipeptidyl peptidase IV relative to the renal arteries of normotensive rats. Collectively, these results demonstrate that the renal acute responses to GLP-1 are attenuated in SHRs. Thus, chronic treatment with incretin-based agents may rely upon the upregulation of GLP-1/GLP-1 receptor signaling in the kidneys of hypertensive patients and experimental models. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/28576404/Attenuated_diuresis_and_natriuresis_in_response_to_glucagon_like_peptide_1_in_hypertensive_rats_are_associated_with_lower_expression_of_the_glucagon_like_peptide_1_receptor_in_the_renal_vasculature_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30386-2 DB - PRIME DP - Unbound Medicine ER -