Interactions Between Sympathetic Nervous System and Endogenous Endothelin in Patients With Essential Hypertension

被引:58
作者
Bruno, Rosa Maria [1 ]
Sudano, Isabella [2 ]
Ghiadoni, Lorenzo [1 ]
Masi, Lorenzo [1 ]
Taddei, Stefano [1 ]
机构
[1] Univ Pisa, Dept Internal Med, I-56100 Pisa, Italy
[2] Univ Zurich Hosp, Cardiovasc Ctr Cardiol, CH-8091 Zurich, Switzerland
关键词
hypertension; sympathetic nervous system; endothelin; microneurography; BQ123; RECEPTOR ANTAGONISM; BLOOD-PRESSURE; CONSCIOUS RATS; MENTAL STRESS; VASOCONSTRICTION; NORADRENALINE; BAROREFLEX; ACTIVATION; BQ-123;
D O I
10.1161/HYPERTENSIONAHA.110.163584
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Experimental evidence indicates that endothelin 1 stimulates the sympathetic nervous system by activation of the subtype A receptor. The aim of the present study was to assess whether this mechanism is active in humans and to investigate its potential role in the pathogenesis of essential hypertension. In 15 hypertensive patients and 12 normotensive subjects, blood pressure, heart rate, and muscle sympathetic nerve activity were evaluated during intravenous 20-minute infusion of BQ123 (0.1 mg/kg per hour), an endothelin A receptor antagonist, and sodium nitroprusside (SNP; 0.4 mu g/kg per minute). In hypertensive patients, blood pressure was reduced similarly by BQ123 and SNP. In contrast, the increase in muscle sympathetic nerve activity induced by BQ123 (from 52.0 +/- 4.9 to 56.8 +/- 5.5 bursts per 100 heartbeats; P<0.05 versus baseline) was significantly lower (P<0.05) than that induced by SNP (from 50.6 +/- 4.9 to 61.1 +/- 5.1 bursts per 100 heartbeats; P<0.05 versus baseline). In normotensive subjects, SNP reduced blood pressure and increased muscle sympathetic activity, whereas BQ123 was ineffective. Thus, in a subgroup (n=9) of normotensive subjects, we administered BQ123 at a higher dose (0.2 mg/kg per hour), representing an equidepressor dose of SNP, inducing a blunted increase in sympathetic activity (from 44.1 +/- 2.4 to 50.1 +/- 6.4 bursts per 100 heartbeats; P<0.05 versus baseline). Finally, administration of a different vasodilator (papaverine, 0.5 mg/kg per hour) exerted results superimposable to SNP. Endogenous endothelin 1 appears to have a sympathoexcitatory effect both in normotensive and hypertensive subjects through endothelin A receptors, contributing to basal sympathetic vasomotor tone. Moreover, essential hypertension shows an increased susceptibility to the sympathoexcitatory effect of endogenous endothelin 1. (Hypertension. 2011; 57:79-84.)
引用
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页码:79 / 84
页数:6
相关论文
共 27 条
[1]   Role of endothelin in the increased vascular tone of patients with essential hypertension [J].
Cardillo, C ;
Kilcoyne, CM ;
Waclawiw, M ;
Cannon, RO ;
Panza, JA .
HYPERTENSION, 1999, 33 (02) :753-758
[2]   GENERAL CHARACTERISTICS OF SYMPATHETIC ACTIVITY IN HUMAN MUSCLE NERVES [J].
DELIUS, W ;
HAGBARTH, KE ;
WALLIN, BG ;
HONGELL, A .
ACTA PHYSIOLOGICA SCANDINAVICA, 1972, 84 (01) :65-&
[3]   Role of endothelin-1 in clinical hypertension - 20 years on [J].
Dhaun, Neeraj ;
Goddard, Jane ;
Kohan, Donald E. ;
Pollock, David M. ;
Schiffrin, Ernesto L. ;
Webb, David J. .
HYPERTENSION, 2008, 52 (03) :452-459
[4]   TOTAL, AND ORGAN-SPECIFIC, NORADRENALINE PLASMA KINETICS IN ESSENTIAL-HYPERTENSION [J].
ESLER, M ;
JENNINGS, G ;
KORNER, P ;
BLOMBERY, P ;
BURKE, F ;
WILLETT, I ;
LEONARD, P .
CLINICAL AND EXPERIMENTAL HYPERTENSION PART A-THEORY AND PRACTICE, 1984, 6 (1-2) :507-521
[5]   Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure - A comparison of selective and combined endothelin receptor blockade [J].
Goddard, J ;
Johnston, NR ;
Hand, MF ;
Cumming, AD ;
Rabelink, TJ ;
Rankin, AJ ;
Webb, DJ .
CIRCULATION, 2004, 109 (09) :1186-1193
[6]   Baroreflex control of sympathetic nerve activity in essential and secondary hypertension [J].
Grassi, G ;
Cattaneo, BM ;
Seravalle, G ;
Lanfranchi, A ;
Mancia, G .
HYPERTENSION, 1998, 31 (01) :68-72
[7]   Comparison between reproducibility and sensitivity of muscle sympathetic nerve traffic and plasma noradrenaline in man [J].
Grassi, G ;
Bolla, G ;
Seravalle, G ;
Turri, C ;
Lanfranchi, A ;
Mancia, G .
CLINICAL SCIENCE, 1997, 92 (03) :285-289
[8]   Role of sympathetic nervous system in cardiovascular effects of centrally administered endothelin-1 in rats [J].
Gulati, A ;
Rebello, S ;
Kumar, A .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1997, 273 (03) :H1177-H1186
[9]   DIRECT AND SYMPATHETICALLY MEDIATED VENOCONSTRICTION IN ESSENTIAL-HYPERTENSION - ENHANCED RESPONSES TO ENDOTHELIN-1 [J].
HAYNES, WG ;
HAND, MF ;
JOHNSTONE, HA ;
PADFIELD, PL ;
WEBB, DJ .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (04) :1359-1364
[10]   DETERMINATION OF PLASMA-CATECHOLAMINES BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION - COMPARISON WITH A RADIOENZYMATIC METHOD [J].
HJEMDAHL, P ;
DALESKOG, M ;
KAHAN, T .
LIFE SCIENCES, 1979, 25 (02) :131-138