Abstract
Left ventricular hypertrophy (LVH) is associated with decreased responsiveness of renal α1-adrenoreceptors subtypes to adrenergic agonists. Nitric oxide donors are known to have antihypertrophic effects however their impact on responsiveness of renal α1-adrenoreceptors subtypes is unknown. This study investigated the impact of nitric oxide (NO) and its potential interaction with the responsiveness of renal α1-adrenoreceptors subtypes to adrenergic stimulation in rats with left ventricular hypertrophy (LVH). This study also explored the impact of NO donor on CSE expression in normal and LVH kidney. LVH was induced using isoprenaline and caffeine in drinking water for 2 weeks while NO donor (L-arginine, 1.25g/Lin drinking water) was given for 5 weeks. Intrarenal noradrenaline, phenylephrine and methoxamine responses were determined in the absence and presence of selective α1-adrenoceptor antagonists, 5- methylurapidil (5-MeU), chloroethylclonidine (CeC) and BMY 7378. Renal cortical endothelial nitric oxide synthase mRNA was upregulated 7 fold while that of cystathione γ lyase was unaltered in the NO treated LVH rats (LVH-NO) group compared to LVH group. The responsiveness of renal α1A, α1B and α1D-adrenoceptors in the low dose and high dose phases of 5-MeU, CEC and BMY7378 to adrenergic agonists was increased along with cGMP in the kidney of LVH-NO group. These findings suggest that exogenous NO precursor up-regulated the renal eNOS/NO/cGMP pathway in LVH rats and resulted in augmented α1A, α1B and α1D adrenoreceptors responsiveness to the adrenergic agonists. There is a positive interaction between H2S and NO production in normal animals but this interaction appears absent in LVH animals.
Highlights
Left ventricular hypertrophy (LVH) is characterized by overstimulation of the heart due to hyperactivity of the sympathetic nervous system and both circulating noradrenaline and mean discharge frequency in peripheral sympathetic nerves have been reported elevated in hypertensive LVH patients [1].At an experimental level, renal sympathetic nerve activity was found to be elevated in rats with essential hypertension and LVH compared to the control Wistar Kyoto rats [2]
Previous studies have shown that nitric oxide (NO) increased papillary blood perfusion [15], the present study demonstrated that this occurred in the renal cortex as renal cortical blood perfusion was increased at a time when the endothelial nitric oxide synthase (eNOS)/NO/cGMP pathway was up regulated in the cortex of the kidney
The present study explored whether there was a down regulation of eNOS/NO/ cGMP pathway in the kidney of LVH rats
Summary
Left ventricular hypertrophy (LVH) is characterized by overstimulation of the heart due to hyperactivity of the sympathetic nervous system and both circulating noradrenaline and mean discharge frequency in peripheral sympathetic nerves have been reported elevated in hypertensive LVH patients [1].At an experimental level, renal sympathetic nerve activity was found to be elevated in rats with essential hypertension and LVH compared to the control Wistar Kyoto rats [2] This sympatho-activation is associated with vascular dysfunction and impairment of α1-adrenoceptor-mediated renal vasoconstriction [3].This attenuation of α1-adrenoceptormediated renal vasoconstrictor responsiveness to adrenergic agonists in states of hypertension and renal failure has been studied previously [4]. Increased vasoconstriction due to elevated NA and Ang II can be suppressed as a result of an up-regulation of the NO-cGMP pathway which is responsible for inhibition of L-type Ca2+ channels [10] which induce a vasodilation
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