title: Nucleus of the solitary tract (pro)renin receptor-mediated antihypertensive effect involves nuclear factor-κB-cytokine signaling in the spontaneously hypertensive rat.
abstract: The importance of the (pro)renin receptor (PRR) in the function of the central nervous system is increasingly evident because PRR seems to play a role in neuronal control of cardiovascular function. PRR expression is elevated in the nucleus of the solitary tract (NTS) of spontaneously hypertensive rats (SHR). In this study, we tested the hypothesis that altered activity of PRR in the NTS is linked to hypertension. Eight weeks of chronic knockdown of the NTS PRR, using recombinant adeno-associated virus type 2 (AAV2)-PRR-small hairpain RNA (shRNA)-mediated gene transduction, caused a significant increase in mean arterial pressure (MAP) in the SHR (shRNA, 173±5; Control, 151±6 mm Hg) but not in Wistar Kyoto rats (shRNA, 108±7; Control, 106±6 mm Hg). The MAP elevation in the SHR was associated with decreased inflammatory markers tumor necrosis factor-α, interleukin-6, C-C motif ligand 5, and their transcription factor, nuclear factor-κB. Consistent with the pressor effects of the PRR knockdown, acute bilateral NTS injection of human renin (2 pmol/side) decreased MAP and heart rate (HR) in SHR (ΔMAP, -38±4 mm Hg; Δheart rate, -40±10 bpm), with negligible responses in Wistar Kyoto rats (ΔMAP, -4±3 mm Hg; Δheart rate, -12±7 bpm). These effects in SHR were attenuated (80%) by prorenin handle region peptide but were not affected by angiotensin II type 1 or angiotensin II type 2 receptor blockers. Finally, PRR activation in SHR neuronal cultures by prorenin activated nuclear factor-κB and increased mRNA levels of interleukin-1β (250-fold), tumor necrosis factor-α (32-fold), interleukin-6 (35-fold), C-C motif ligand 5 (12-fold), and interleukin-10 (7-fold) in a nuclear factor-κB-dependent but angiotensin II type 1 receptor-independent manner. Therefore, NTS PRR mediates antihypertensive effects via an angiotensin II-independent mechanism in SHR, which involves stimulation of the nuclear factor-κB-cytokine signaling pathway.
authors: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
authors: Jasenka
authors: J
authors: Zubcevic
authors: Joo Y
authors: JY
authors: Jun
authors: Gwyneth
authors: G
authors: Lamont
authors: Tatiane M
authors: TM
authors: Murça
authors: Peng
authors: P
authors: Shi
authors: Wei
authors: W
authors: Yuan
authors: Fan
authors: F
authors: Lin
authors: Jessica Marulanda
authors: JM
authors: Carvajal
authors: Qiuhong
authors: Q
authors: Li
authors: Colin
authors: C
authors: Sumners
authors: Mohan K
authors: MK
authors: Raizada
authors: Zhiying
authors: Z
authors: Shan
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D057912:Angiotensin II Type 2 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D020868:Gene Silencing; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012083:Renin / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000093342:Prorenin Receptor
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D016207:Cytokines; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D012083:Renin; D000093342:Prorenin Receptor