The interaction between renin angiotensin system and sympathetic nervous system in the renal vasculature of normal and hyperte
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Date
2009-04
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Abstract
Interactions between the renin-angiotensin system (RAS) and sympathetic nervous
system (SNS) have recently been the subject of much interest. This study was aimed to
examine the adrenergic interactions of intrarenal arterially administered angiotensin II
and a set of adrenergic agonists in normal and hypertensive rats. Wi star-Kyoto (WKY)
and spontaneously hypertensive rats (SHR) were subjected to 7 days treatment with
either losartan (lOmg/kg/day), carvedilol (5mg/kg/day) or losartan plus carvedilol
(lOmglkg/day+5mg/kg/day), in day 8, rats were anesthetized and renal vasoconstrictor/
vasodilator study was performed. A group of rats was SUbjected to acute unilateral renal
denervation of the left kidney. The changes in the renal vascular responses were
determined in terms of reductions or elevations in renal blood flow caused by renal
nerve stimulation (RNS), noradrenaline (NA), phenylephrine (PE), methoxamine (ME),
angiotensine II (Ang II), dopamine (Dop) and isoprenaline (Jsop). The mean arterial
pressure (MAP) and renal blood flow (RBF) were continuously monitored throughout
the experiment. The data were represented as meansĀ±S.E.M. and were analyzed with
one- and two-way ANOV A with a significance level of 5%. Baseline values of MAP
and RBF remained consistent throughout the study except in few groups. Data showed
augmented renal responsiveness to the vasoactive agents after denervation. Moreover,
there was a significant (P<O.05) fall in the vascular responses to Ang II and adrenergic
agonists after losartan treatment in SHR. Data from rats treated with carvedilol showed
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significant (P<O.05) reductions in the vasoconstrictor responses to Ang II along with all
the adrenergic agonists given. Losartan plus carvedilol treated SHR showed a significant
(P<O.05) reduction in the renal vascular responsiveness to Ang II, NA, PE and Dop.
While, significant enhancement (P<O.05) in responses to NA, PE and ME was observed
in WKY rats. In losartan, carvedilol and losartan plus carvedilol treated denervated
SHR, there was a significant (P<O.05) blunting of the responses to neural stimuli and
vasoactive agents as compared to untreated denervated SHR. These data suggest an
enhanced sensitivity of ul-adrenoceptors to adrenergic agonists and possible
enhancement of AT I receptors functionality in the renal vasculature of these rats.
Moreover, renal vasoconstriction induced by Ang II is contributed to by adrenergic
action which is not dependent on intact renal innervation. The use of losartan plus
carvedilol has no additional depressant effect for renal responses to Ang II while it has
aggravating effect for these responses to adrenergic agonists and this indeed indicates a
positive cross talk between RAS and SNS.
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Keywords
Interactions between the renin-angiotensin system (RAS) and sympathetic nervous system (SNS) , have recently been the subject of much interest.