Antihypertensive effect of thromboxane A2 receptor blockade in genetically hypertensive rats of the Lyon strain

Geoffroy, J; Benzoni, Daniel; Sassard, J

doi:10.1097/00004872-198900076-00132

Cited by 13 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thromboxane is widely known as a key inflammatory substance that mediates vascular smooth muscle cells contraction and proliferation via the TP receptor [30,31]. The TP receptor density has been reported to be enhanced in cardiovascular disease [32] and in hypertension [33]. Previous investigations have revealed that TP generation is increased in aortic segments of cholesterol‐fed atherosclerotic rabbits [34], and that in two transgenic murine models of atherogenesis the TP biosynthesis is elevated [35].…”

Section: Discussionmentioning

confidence: 99%

Up‐Regulation of G‐Protein‐Coupled Receptors for Endothelin and Thromboxane by Lipid‐Soluble Smoke Particles in Renal Artery of Rat

Xie

Wang

Zhang

et al. 2010

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Up-regulation of G-protein-coupled receptors (GPCR) plays key roles in renal hypertension and cardiovascular disease pathogenesis. The present study was designed to examine if lipid-soluble cigarette smoking particles (DSP), nicotine and endotoxin (LPS), induce GPCR up-regulation for thromboxane A 2 (TP), endothelin type A (ET A ) and type B (ET B ) receptors in renal artery, and if intracellular signal mechanisms are involved. Renal artery segments of rats were exposed to DSP, nicotine or LPS, in organ culture for up to 24 hr. The GPCR-mediated contractions were recorded by using a myograph system. Expression of the GPCR was examined by real-time PCR and immunohistochemistry at mRNA and protein levels. Sarafatoxin 6c (S6c, selective ET B receptor agonist), endothelin-1 (ET-1, non-selective ET A and ET B receptor agonist) and 9,11-Dideoxy-9a,11a-methanoepoxy prostaglandin F 2a (U46619, a TP receptor agonist) induced contractions were significantly increased after the arterial segments exposed to DSP in a concentration-dependent (0.1-0.4 ll ⁄ ml) manner, and S6c also induced a time-dependent contraction, compared to control (dimethyl sulfoxide). This was in parallel with enhanced mRNA expression for ET B receptor but not ET A and TP receptors, while increased protein expression for ET A , ET B and TP receptors was seen. The specific nuclear factor-kappa B (NF-jB) signal pathway inhibitor BMS345541 was applied to link DSP effects to the GPCR up-regulation. It totally abolished ET B receptor up-regulation, but not ET A and TP receptor up-regulations. Our results suggest that DSP transcriptionally up-regulated ET B receptor expression in rat renal artery via NF-jB signal pathways, whereas up-regulation of ET A and TP receptor-mediated contraction may involve post-transcriptional mechanisms.Both active and passive cigarette smoking is a well-known risk factor for hypertension, atherosclerosis (AS), coronary heart disease (CHD), stroke, myocardial infarction, aortic aneurysm, peripheral vascular disease and other cardiovascular diseases [1]. In a previous study, we demonstrated that lipid-soluble cigarette smoking particles (DSP) cause damage to vascular endothelial cells and vascular smooth muscle cells [2] reduce the formation and release of prostacyclin from [3,4]. DSP may also have a direct toxic effect on vascular endothelial cells and reduce endothelium-dependent dilatation in rat mesenteric arteries and human middle cerebral arteries [5]. As a complex, DSP consist of more than 4000 different substances. Among them, nicotine and endotoxin (LPS) are important substances contained in cigarette smoke, which may induce damage to the cardiovascular system. The up-regulation of G-protein-coupled receptors (GPCR) for endothelin type B (ET B ) receptors in arteries is suggested to be one of key mechanisms that cigarette smoke leads to cardiovascular disease [6]. The intracellular signal pathways activated by DSP involve activation of mitogenactivated protein kinase and the downstream transcriptional factor nuc...

show abstract

Section: Discussionmentioning

confidence: 99%

Up‐Regulation of G‐Protein‐Coupled Receptors for Endothelin and Thromboxane by Lipid‐Soluble Smoke Particles in Renal Artery of Rat

Xie

Wang

Zhang

et al. 2010

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…It demonstrates that the increased renal synthesis of TxA 2 observed in vivo in young LH rats reflects an elevated activity of the Tx synthetase, which is revealed by extfarenal stimuli such as adrenergic receptor activation. Because TxA 2 /PGH 2 receptor blockade, which has been shown to decrease the blood pressure of LH rats, 11 also depresses the effects of a-adrenergic receptor stimulation in the isolated kidneys, the above described abnormality is likely to be involved in the pathogenesis of hypertension in that model.…”

Section: Figure 4 Graphs Showing Effects Of Thromboxane Ajprostaglanmentioning

confidence: 99%

“…This hypothesis is supported by the observation that TxA 2 synthesis inhibition or blockade of TxA 2 receptors delays the onset 9 or reduces 10 the severity of hypertension in SHR and in LH rats. 11 However, the mechanisms underlying the TxA 2 increase remain to be elucidated. Among them, the sympathetic nervous system could be of major importance since 1) intrarenal administration of norepinephrine (NE) and of phenylephrine (PHE) 12 - 13 or electrical renal nerve stimulation 14 is followed by an increase in prostaglandin synthesis and 2) the in vivo turnover of norepinephrine is increased in the kidney cortex of 5-week-old LH rats.…”

mentioning

confidence: 99%

Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat.

et al. 1991

View full text Add to dashboard Cite

Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B 2 when compared with nonnotensive (LN) and low blood pressure (LL) controls. Therefore, the effects of norepinephrine (1.2 xlO" 8 to 9.6 xlO" 7 M) and of phenylephrine (5xlO~8 to 1.9x10"' M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed before and during thromboxane A 2 /prostaglandin H 2 receptor blockade by AH23848 (4xlO~* M). Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E 2 and F^, of 6-ketoprostaglandin F la , and of thromboxane B 2 was similar in the three strains. The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced. Norepinephrine and phenylephrine induced a 10-to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B 2 only. AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys. In conclusion, isolated perfused kidneys from LH rats exhibit an increased production of thromboxane A 2 , which enhances the renal effects of norepinephrine and therefore could participate in the development of hypertension of the Lyon model. (Hypertension 1991;17:296-302)

show abstract

“…Tx is involved in blood platelet function and linked with hemostasis and thrombosis [12,13]. The TP receptors density has been reported to be enhanced in cardiovascular disease [14] and in hypertension [15]. Previous experimental and clinical data have demonstrated that treatment with a TP receptor antagonist (e.g.…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of thromboxane A2 receptor expression by lipid soluble smoking particles through post-transcriptional mechanisms

Zhang

Edvinsson

et al. 2008

Atherosclerosis

View full text Add to dashboard Cite

Antihypertensive effect of thromboxane A2 receptor blockade in genetically hypertensive rats of the Lyon strain

Cited by 13 publications

References 0 publications

Up‐Regulation of G‐Protein‐Coupled Receptors for Endothelin and Thromboxane by Lipid‐Soluble Smoke Particles in Renal Artery of Rat

Up‐Regulation of G‐Protein‐Coupled Receptors for Endothelin and Thromboxane by Lipid‐Soluble Smoke Particles in Renal Artery of Rat

Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat.

Up-regulation of thromboxane A2 receptor expression by lipid soluble smoking particles through post-transcriptional mechanisms

Contact Info

Product

Resources

About