Abstract
The incidence of chronic kidney disease (CKD) is increasing worldwide, with more than 26 million people suffering from CKD in the United States alone. More patients with CKD die of cardiovascular complications than progress to dialysis. Over 80% of CKD patients have hypertension, which is associated with increased risk of cardiovascular morbidity and mortality. Another common, perhaps underappreciated, feature of CKD is an overactive sympathetic nervous system. This elevation in sympathetic nerve activity (SNA) not only contributes to hypertension but also plays a detrimental role in the progression of CKD independent of any increase in blood pressure. Indeed, high SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure. This brief review will discuss some of the consequences of sympathetic overactivity and highlight some of the potential pathways contributing to chronically elevated SNA in CKD. Mechanisms leading to chronic sympathoexcitation in CKD are complex, multifactorial and to date, not completely understood. Identification of the mechanisms and/or signals leading to sympathetic overactivity in CKD are crucial for development of effective therapeutic targets to reduce the increased cardiovascular risk in this patient group.
Highlights
More than 26 million people in the United States suffer from chronic kidney disease (CKD) with thousands of new cases diagnosed each year [1]
In agreement with a time delay in sympathetic activation via systemic nitric oxide synthase (NOS) inhibition, when phentolamine (α-adrenergic blocker) was infused immediately and 90 min after L-nitroarginine methyl ester (L-NAME) infusion in humans, there was little effect on the initial hypertensive response but phentolamine significantly attenuated the subsequent further increase in blood pressure [76]. These results indicate that the initial increase in blood pressure occurred due to diminished peripheral nitric oxide (NO) causing inhibition of endothelium-mediated vasodilation while the later increase in blood pressure was caused by sympathetic adrenergic vasoconstriction
This would explain the results observed in initial studies where NOS inhibition caused a reduction in sympathetic nerve activity (SNA), as SNA was only measured for 40 min after L-NAME infusion [86], which may not have been long enough to observe central effects of systemic NOS inhibition
Summary
More than 26 million people in the United States suffer from chronic kidney disease (CKD) with thousands of new cases diagnosed each year [1]. There is growing evidence that sympathetic overactivity, a characteristic feature of CKD, is one of the major mechanisms leading to higher CV risk in this patient population [9,10]. Observations of exaggerated SNA in renal failure patients came from studies showing significantly elevated plasma. Observation2sof o18f exaggerated SNA in renal failure patients came from studies showing significantly elevated plasma norepinephrine, the primary neurotransmitter released by sympathetic nerves [16,17]. OOrriiggiinnaall rreeccoorrdd ooff mmuussccllee ssyymmppaatthheettiicc nneerrvvee aaccttiivviittyy ((MMSSNNAA)) iinn aa nnoorrmmaall ssuubbjjeecctt aanndd aa rreennaall ffaailiulurreepaptaietinetnot nohnemheomdioadlyiasilsy,sdise,mdoenmstornatsitnragtsiniggnisfiigcanniftilcyagnrtelyategrrereastteirngreMstSinNgAMinStNhAe diinalytshies pdaiatileynsits. MMuussccllee ssyymmppaatthheettiicc nneerrvvee aaccttiivviittyy ((MMSSNNAA)) eexxpprreesssseedd aass bbuurrsstt ffrreeqquueennccyy ((bbuurrssttss ((bbss))//mmiinn,, AA)) aanndd bbuurrsstt iinncciiddeennccee ((bbss//110000 hheeaarrttbbeeaattss ((hhbb)),, BB)) iinn ssuubbjjeeccttss ggrroouuppeedd aaccccoorrddiinngg ttoo tthheeiirr eessttiimmaatteedd gglloommeerruullaarr ffiillttrraattiioonn rraattee((eeGGFFRR)),,wwitihthththeehhigighhesetstququaratritleileofoefGeGFRFRiningrgoruopupI aInadnldowloewsteqstuqarutailretiolef eoGf eFGRFiRn ignroguropuIpVI.VW. WithithdedcerceraesaisnigngeGeGFRFR, t,hthereereisisaassigignnifiificcaannttaannddpprrooggrreessssiivvee iinnccrreeaassee iinn rreessttiinngg MMSSNNAA iinn cchhrroonniicc kkiiddnneeyy ddiisseeaassee ((CCKKDD)) ppaattiieennttss.. ** pp
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