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Renal vascular relaxation response to glucagon‐like peptide‐1 (GLP‐1) is impaired in spontaneously hypertensive rats (SHR)
Author(s) -
Crajoinas Renato Oliveira,
Savignano Fernanda Alcantara,
Nakamuta Juliana Sanajotti,
Girardi Adriana C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.688.2
Subject(s) - medicine , endocrinology , vasodilation , kidney , renal artery , vascular smooth muscle , hemodynamics , artery , smooth muscle
Research in our laboratory and others have established that GLP‐1 causes diuresis and natriuresis in normotensive animals by means of tubular and hemodynamic mechanisms. Interestingly, we have recently observed that GLP‐1 does not affect renal hemodynamics in SHR. The aim of the present study was to evaluate the renal vascular effects of GLP‐1 on normotensive and hypertensive rats. By means of immunofluorescence, we verified that the GLP‐1 receptor (GLP‐1R) colocalized with endothelial and smooth muscle cell markers in renal arteries from both rat strains. However, it was noted that 100 nM GLP‐1 induced vasodilation in isolated renal arterial rings through an endothelial‐independent mechanism only in Wistar rats, and did not alter vascular reactivity in renal arteries from SHR. The lack of a vasodilator effect of GLP‐1 was not due to decreased expression of GLP‐1R in renal arteries from SHR. Besides, we observed that the activity and expression of the enzyme dipeptidyl peptidase IV (DPPIV), responsible for GLP‐1 degradation, was significantly increased in the renal artery of SHR vs. Wistar. Furthermore, although there was no difference in basal concentrations of cAMP between renal arteries of Wistar and SHR, incubation of these vessels with GLP‐1 significantly raised cAMP concentration only in renal arterial rings from Wistar, while in the SHR cAMP concentration remained similar to baseline. These data suggest that GLP‐1 has a vasodilator effect in the Wistar renal artery through binding to its receptor and elevation of vascular smooth muscle cAMP. In addition, renal arteries from SHR do not respond to GLP‐1‐mediated vasorelaxation, at least in part due to higher levels of DPPIV activity and expression, and/or by an alteration in the signaling processes that link GLP‐1R activation with the stimulation of adenylyl cyclase. Support: FAPESP