The effects of bradykinin B1 receptor antagonism on the myocardial and vascular consequences of hypertension in SHR rats

Laszlo Deres, Krisztian Eros, Orsolya Horvath, Noemi Bencze, Csongor Cseko, Sandor Farkas, Tamas Habon, K. Tóth, R. Halmosi

Research output: Contribution to journalArticle

Abstract

It is known that non-steroidal anti-inflammatory drugs increase cardiovascular (CV) morbidity and mortality. In this study, we examined whether a novel anti-inflammatory drug, bradykinin B1 receptor antagonist (FGY-1153) treatment could influence the development of hypertensive organ damages in spontaneously hypertensive rats (SHR). SHRs were treated with low (FGY-120) or high dose FGY-1153 (FGY-400) and with placebo (Control) for 26 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY). Body weight, food consumption and blood pressure were measured regularly. Echocardiography was performed at the beginning and at the end of the study. Light and electron microscopic analysis of heart and great vessels were performed, and the extent of fibrotic areas was measured. The phosphorylation state of prosurvival Akt-1/glycogen synthase kinase (GSK)-3β pathway and the activation of signaling factors playing part in the fibrotic processes - mitogen activated protein kinases (MAPKs), and TGF-β/Smad2 - were monitored using Western-blot. Body weight and food consumption as well as the elevated blood pressure in SHRs was not influenced by FGY-1153 treatment. However, both doses of FGY-1153 treatment decreased left ventricular (LV) hypertrophy and diastolic dysfunction in hypertensive animals. Moreover systolic LV function was also preserved in FGY-120 group. Increased intima-media thickness and interstitial fibrosis were not significantly diminished in great vessels. FGY-1153 treatment inhibited the expression of TGFβ and the phosphorylation of SMAD2 in the heart. Our results suggest that the tested novel anti-inflammatory compound has no deleterious effect on CV system, moreover it exerts moderate protective effect against the development of hypertensive cardiopathy.

Original languageEnglish
Article number624
JournalFrontiers in Physiology
Volume10
Issue numberMAY
DOIs
Publication statusPublished - Jan 1 2019

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Bradykinin B1 Receptors
Inbred SHR Rats
Blood Vessels
Hypertension
Anti-Inflammatory Agents
Body Weight
Phosphorylation
Blood Pressure
Glycogen Synthase Kinase 3
Cardiovascular Agents
Food
Inbred WKY Rats
Left Ventricular Hypertrophy
Therapeutics
Cardiovascular System
Mitogen-Activated Protein Kinases
Left Ventricular Function
Echocardiography
Fibrosis
Western Blotting

Keywords

  • Bradykinin B1 receptor antagonism
  • Cardiovascular remodeling
  • Echocardiography
  • Hypertensive target organ damages
  • NSAIDs
  • Spontaneously hypertensive rats

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

The effects of bradykinin B1 receptor antagonism on the myocardial and vascular consequences of hypertension in SHR rats. / Deres, Laszlo; Eros, Krisztian; Horvath, Orsolya; Bencze, Noemi; Cseko, Csongor; Farkas, Sandor; Habon, Tamas; Tóth, K.; Halmosi, R.

In: Frontiers in Physiology, Vol. 10, No. MAY, 624, 01.01.2019.

Research output: Contribution to journalArticle

Deres, Laszlo ; Eros, Krisztian ; Horvath, Orsolya ; Bencze, Noemi ; Cseko, Csongor ; Farkas, Sandor ; Habon, Tamas ; Tóth, K. ; Halmosi, R. / The effects of bradykinin B1 receptor antagonism on the myocardial and vascular consequences of hypertension in SHR rats. In: Frontiers in Physiology. 2019 ; Vol. 10, No. MAY.
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AU - Cseko, Csongor

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