Interactions between sympathetic nervous system and endogenous endothelin in patients with essential hypertension.
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 μg/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.
Department of Internal Medicine, University of Pisa, Pisa, Italy. rosam.bruno@gmail.com
Rosa Maria
RM
Bruno
Isabella
I
Sudano
Lorenzo
L
Ghiadoni
Lorenzo
L
Masi
Stefano
S
Taddei
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000294:innervation / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D009599:Nitroprusside; D010208:Papaverine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)