PMID- 30940538
OWN - NLM
STAT- MEDLINE
DCOM- 20190513
LR  - 20190513
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 225
DP  - 2019 May 15
TI  - Chronic administration of sildenafil improves endothelial function in 
      spontaneously hypertensive rats by decreasing COX-2 expression and oxidative 
      stress.
PG  - 29-38
LID - S0024-3205(19)30244-9 [pii]
LID - 10.1016/j.lfs.2019.03.074 [doi]
AB  - AIMS: Spontaneously hypertensive rats (SHR) exhibit impaired endothelial 
      vasodilation and enhanced vasoconstriction. The phosphodiesterase 5 (PDE5) 
      inhibitor sildenafil (Sild) potentiates the nitric oxide (NO)-mediated effects 
      exerting antioxidative and anti-inflammatory actions. In the present study, we 
      hypothesized that Sild could improve endothelial function in SHR. MATERIALS AND 
      METHODS: Male rats were treated daily for 60 days by oral gavage with Sild 
      (45 mg/kg) before the onset of the hypertensive state (pre-hypertensive 
      protocol). The aortic relaxation to acetylcholine (ACh), sodium nitroprusside 
      (SNP) and the phenylephrine (Phe)-induced contraction was evaluated in SHR. 
      Protein expression of eNOS, p-eNOS, caveolin, COX-1, COX-2, ERK and p-ERK was 
      measured by Western blot. KEY FINDINGS: Resting blood pressure was not modified 
      by Sild administration. Treatment with Sild did not alter the relaxation response 
      to SNP but improved the ACh-induced relaxation and reduced Phe-induced 
      contraction in aortic rings from SHR. This protective effect of Sild could be 
      attributed to reduced superoxide anions (O(2)(-)) generation, cyclooxygenase type 
      2 (COX-2) protein downregulation and increased NO bioavailability. SIGNIFICANCE: 
      Sild improves endothelial function in SHR aorta without affecting resting blood 
      pressure values. These results indicate that PDE5 inhibition has a potential role 
      in the improvement of vascular function and could be an adjuvant in the treatment 
      of essential hypertension.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Teixeira-da-Silva, Jose Jairo
AU  - Teixeira-da-Silva JJ
AD  - Departamento de Fisiologia e Farmacologia, Centro de Biociencias, Universidade 
      Federal de Pernambuco, Recife 50670-901, PE, Brazil.
FAU - Nunes-Moreira, Hicla Stefany
AU  - Nunes-Moreira HS
AD  - Departamento de Fisiologia e Farmacologia, Centro de Biociencias, Universidade 
      Federal de Pernambuco, Recife 50670-901, PE, Brazil.
FAU - Silva, Cristina Oliveira
AU  - Silva CO
AD  - Nucleo de Nutricao, Centro Academico de Vitoria, Universidade Federal de 
      Pernambuco, Recife 55608-680, PE, Brazil.
FAU - Lahlou, Saad
AU  - Lahlou S
AD  - Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade 
      Federal do Ceara, Fortaleza 60430-270, CE, Brazil.
FAU - Naro, Fabio
AU  - Naro F
AD  - Dipartimento di Scienze Anatomiche, Istologiche, Medico-legali e dell'Apparato 
      Locomotore, Universita di Roma - Sapienza, Rome 00161, Italy.
FAU - Xavier, Fabiano Elias
AU  - Xavier FE
AD  - Departamento de Fisiologia e Farmacologia, Centro de Biociencias, Universidade 
      Federal de Pernambuco, Recife 50670-901, PE, Brazil.
FAU - Duarte, Gloria Pinto
AU  - Duarte GP
AD  - Departamento de Fisiologia e Farmacologia, Centro de Biociencias, Universidade 
      Federal de Pernambuco, Recife 50670-901, PE, Brazil. Electronic address: 
      duarteg@ufpe.br.
LA  - eng
PT  - Journal Article
DEP - 20190330
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Vasodilator Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Ptgs2 protein, rat)
SB  - IM
MH  - Animals
MH  - Cardiomegaly/*prevention & control
MH  - Cells, Cultured
MH  - Cyclooxygenase 2/*chemistry/metabolism
MH  - Endothelium, Vascular/*drug effects/metabolism/pathology
MH  - Hypertension/*drug therapy/metabolism/pathology
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Sildenafil Citrate/*administration & dosage
MH  - Vasodilator Agents/*administration & dosage
OTO - NOTNLM
OT  - Endothelial dysfunction
OT  - Hypertension
OT  - Phosphodiesterase
OT  - Sildenafil
OT  - Vasorelaxation
EDAT- 2019/04/04 06:00
MHDA- 2019/05/14 06:00
CRDT- 2019/04/04 06:00
PHST- 2019/01/05 00:00 [received]
PHST- 2019/03/20 00:00 [revised]
PHST- 2019/03/29 00:00 [accepted]
PHST- 2019/04/04 06:00 [pubmed]
PHST- 2019/05/14 06:00 [medline]
PHST- 2019/04/04 06:00 [entrez]
AID - S0024-3205(19)30244-9 [pii]
AID - 10.1016/j.lfs.2019.03.074 [doi]
PST - ppublish
SO  - Life Sci. 2019 May 15;225:29-38. doi: 10.1016/j.lfs.2019.03.074. Epub 2019 Mar 
      30.