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. 1994 Oct;94(4):1359–1364. doi: 10.1172/JCI117470

Direct and sympathetically mediated venoconstriction in essential hypertension. Enhanced responses to endothelin-1.

W G Haynes 1, M F Hand 1, H A Johnstone 1, P L Padfield 1, D J Webb 1
PMCID: PMC295255  PMID: 7929810

Abstract

Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide. Although circulating concentrations are not increased in essential hypertension, enhanced sensitivity to endothelin-1 has been observed in animal models of hypertension. We investigated dorsal hand vein responses to local infusion of endothelin-1 and norepinephrine in 12 patients with essential hypertension who had never received treatment and in 12 age and sex matched normotensive control subjects. The maximal venoconstriction and the geometric mean of the dose of norepinephrine that caused 50% of maximal venoconstriction were similar in hypertensive (mean +/- SE; 80 +/- 4%; 31 +/- 8 pmol/min) and normotensive subjects (87 +/- 5%, 22 +/- 9 pmol/min). In contrast, mean venoconstriction to endothelin-1 was significantly greater in hypertensive (49 +/- 5%) than in normotensive subjects (27 +/- 2%; P = 0.004). Sympathetically mediated venoconstriction elicited by deep breath was substantially potentiated by endothelin-1 in hypertensive (67 +/- 7% at 90 min) but not normotensive subjects (11 +/- 3% at 90 min; P = 0.001). Venoconstriction to endothelin-1 correlated positively with mean arterial pressure in the hypertensive subjects (r = 0.82; p = 0.001) but negatively in the normotensive subjects (r = -0.58; p = 0.047). Endothelin-1 may contribute to the reduction of venous compliance occurring in the early stages of essential hypertension and to the altered systemic hemodynamics in this condition.

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Selected References

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  1. Abboud F. M., Eckstein J. W. Comparative changes in segmental vascular resistance in response to nerve stimulation and to norepinephrine. Circ Res. 1966 Mar;18(3):263–277. doi: 10.1161/01.res.18.3.263. [DOI] [PubMed] [Google Scholar]
  2. Aellig W. H. A new technique for recording compliance of human hand veins. Br J Clin Pharmacol. 1981 Mar;11(3):237–243. doi: 10.1111/j.1365-2125.1981.tb00527.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson E. A., Sinkey C. A., Lawton W. J., Mark A. L. Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension. 1989 Aug;14(2):177–183. doi: 10.1161/01.hyp.14.2.177. [DOI] [PubMed] [Google Scholar]
  4. Bedarida G., Kim D., Blaschke T. F., Hoffman B. B. Venodilation in Raynaud's disease. Lancet. 1993 Dec 11;342(8885):1451–1454. doi: 10.1016/0140-6736(93)92932-j. [DOI] [PubMed] [Google Scholar]
  5. Benjamin N., Collier J. G., Webb D. J. Angiotensin II augments sympathetically induced venoconstriction in man. Clin Sci (Lond) 1988 Oct;75(4):337–340. doi: 10.1042/cs0750337. [DOI] [PubMed] [Google Scholar]
  6. Browse N. L., Hardwick P. J. The deep-breath-venoconstriction reflex. Clin Sci. 1969 Aug;37(1):125–135. [PubMed] [Google Scholar]
  7. Clarke J. G., Benjamin N., Larkin S. W., Webb D. J., Davies G. J., Maseri A. Endothelin is a potent long-lasting vasoconstrictor in men. Am J Physiol. 1989 Dec;257(6 Pt 2):H2033–H2035. doi: 10.1152/ajpheart.1989.257.6.H2033. [DOI] [PubMed] [Google Scholar]
  8. Clozel M. Endothelin sensitivity and receptor binding in the aorta of spontaneously hypertensive rats. J Hypertens. 1989 Nov;7(11):913–917. doi: 10.1097/00004872-198911000-00011. [DOI] [PubMed] [Google Scholar]
  9. Cockcroft J. R., Chowienczyk P. J., Benjamin N., Ritter J. M. Preserved endothelium-dependent vasodilatation in patients with essential hypertension. N Engl J Med. 1994 Apr 14;330(15):1036–1040. doi: 10.1056/NEJM199404143301502. [DOI] [PubMed] [Google Scholar]
  10. Cockcroft J. R., Clarke J. G., Webb D. J. The effect of intra-arterial endothelin on resting blood flow and sympathetically mediated vasoconstriction in the forearm of man. Br J Clin Pharmacol. 1991 May;31(5):521–524. doi: 10.1111/j.1365-2125.1991.tb05573.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Collier J. G., Lorge R. E., Robinson B. F. Comparison of effects of tolmesoxide (RX71107), diazoxide, hydrallazine, prazosin, glyceryl trinitrate and sodium nitroprusside on forearm arteries and dorsal hand veins of man. Br J Clin Pharmacol. 1978 Jan;5(1):35–44. doi: 10.1111/j.1365-2125.1978.tb01595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Criscione L., Nellis P., Riniker B., Thomann H., Burdet R. Reactivity and sensitivity of mesenteric vascular beds and aortic rings of spontaneously hypertensive rats to endothelin: effects of calcium entry blockers. Br J Pharmacol. 1990 May;100(1):31–36. doi: 10.1111/j.1476-5381.1990.tb12047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davenport A. P., Ashby M. J., Easton P., Ella S., Bedford J., Dickerson C., Nunez D. J., Capper S. J., Brown M. J. A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma: comparison of levels in patients with essential hypertension and normotensive control subjects. Clin Sci (Lond) 1990 Mar;78(3):261–264. doi: 10.1042/cs0780261. [DOI] [PubMed] [Google Scholar]
  14. Deng L. Y., Schiffrin E. L. Effects of endothelin on resistance arteries of DOCA-salt hypertensive rats. Am J Physiol. 1992 Jun;262(6 Pt 2):H1782–H1787. doi: 10.1152/ajpheart.1992.262.6.H1782. [DOI] [PubMed] [Google Scholar]
  15. Dohi Y., Criscione L., Lüscher T. F. Renovascular hypertension impairs formation of endothelium-derived relaxing factors and sensitivity to endothelin-1 in resistance arteries. Br J Pharmacol. 1991 Oct;104(2):349–354. doi: 10.1111/j.1476-5381.1991.tb12434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dohi Y., Lüscher T. F. Endothelin in hypertensive resistance arteries. Intraluminal and extraluminal dysfunction. Hypertension. 1991 Oct;18(4):543–549. doi: 10.1161/01.hyp.18.4.543. [DOI] [PubMed] [Google Scholar]
  17. Eichler H. G., Ford G. A., Blaschke T. F., Swislocki A., Hoffman B. B. Responsiveness of superficial hand veins to phenylephrine in essential hypertension. Alpha adrenergic blockade during prazosin therapy. J Clin Invest. 1989 Jan;83(1):108–112. doi: 10.1172/JCI113845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ellis C. N., Julius S. Role of central blood volume in hyperkinetic borderline hypertension. Br Heart J. 1973 Apr;35(4):450–455. doi: 10.1136/hrt.35.4.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Feldman R. D., Bierbrier G. S. Insulin-mediated vasodilation: impairment with increased blood pressure and body mass. Lancet. 1993 Sep 18;342(8873):707–709. doi: 10.1016/0140-6736(93)91708-t. [DOI] [PubMed] [Google Scholar]
  20. Folkow B. The fourth Volhard lecture: cardiovascular structural adaptation; its role in the initiation and maintenance of primary hypertension. Clin Sci Mol Med Suppl. 1978 Dec;4:3s–22s. doi: 10.1042/cs055003s. [DOI] [PubMed] [Google Scholar]
  21. Haynes W. G., Hamer D. W., Robertson C. E., Webb D. J. Plasma endothelin following cardiac arrest: differences between survivors and non-survivors. Resuscitation. 1994 Mar;27(2):117–122. doi: 10.1016/0300-9572(94)90003-5. [DOI] [PubMed] [Google Scholar]
  22. Haynes W. G., Webb D. J. Endothelium-dependent modulation of responses to endothelin-I in human veins. Clin Sci (Lond) 1993 Apr;84(4):427–433. doi: 10.1042/cs0840427. [DOI] [PubMed] [Google Scholar]
  23. Haynes W. G., Webb D. J. The endothelin family of peptides: local hormones with diverse roles in health and disease? Clin Sci (Lond) 1993 May;84(5):485–500. doi: 10.1042/cs0840485. [DOI] [PubMed] [Google Scholar]
  24. Haynes W. G., Webb D. J. Venoconstriction to endothelin-1 in humans: role of calcium and potassium channels. Am J Physiol. 1993 Nov;265(5 Pt 2):H1676–H1681. doi: 10.1152/ajpheart.1993.265.5.H1676. [DOI] [PubMed] [Google Scholar]
  25. Ishikawa T., Yanagisawa M., Kimura S., Goto K., Masaki T. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. Am J Physiol. 1988 Oct;255(4 Pt 2):H970–H973. doi: 10.1152/ajpheart.1988.255.4.H970. [DOI] [PubMed] [Google Scholar]
  26. Kennedy R. L., Haynes W. G., Webb D. J. Endothelins as regulators of growth and function in endocrine tissues. Clin Endocrinol (Oxf) 1993 Sep;39(3):259–265. doi: 10.1111/j.1365-2265.1993.tb02363.x. [DOI] [PubMed] [Google Scholar]
  27. Kohno M., Murakawa K., Yasunari K., Yokokawa K., Horio T., Kurihara N., Takeda T. Prolonged blood pressure elevation after endothelin administration in bilaterally nephrectomized rats. Metabolism. 1989 Aug;38(8):712–713. doi: 10.1016/0026-0495(89)90054-1. [DOI] [PubMed] [Google Scholar]
  28. Kohno M., Yasunari K., Murakawa K., Yokokawa K., Horio T., Fukui T., Takeda T. Plasma immunoreactive endothelin in essential hypertension. Am J Med. 1990 Jun;88(6):614–618. doi: 10.1016/0002-9343(90)90527-k. [DOI] [PubMed] [Google Scholar]
  29. Komuro I., Kurihara H., Sugiyama T., Yoshizumi M., Takaku F., Yazaki Y. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett. 1988 Oct 10;238(2):249–252. doi: 10.1016/0014-5793(88)80489-7. [DOI] [PubMed] [Google Scholar]
  30. Lüscher T. F., Seo B. G., Bühler F. R. Potential role of endothelin in hypertension. Controversy on endothelin in hypertension. Hypertension. 1993 Jun;21(6 Pt 1):752–757. doi: 10.1161/01.hyp.21.6.752. [DOI] [PubMed] [Google Scholar]
  31. MacLean M. R., McGrath J. C. Effects of endothelin-1 on isolated vascular beds from normotensive and spontaneously hypertensive rats. Eur J Pharmacol. 1990 Nov 6;190(1-2):263–267. doi: 10.1016/0014-2999(90)94137-m. [DOI] [PubMed] [Google Scholar]
  32. Macrae I. M., McAuley M. A., Robinson M. J., Reid J. L., McCulloch J. Endothelin-1-induced hypertension: a consequence of medullary ischemia? J Cardiovasc Pharmacol. 1991;17 (Suppl 7):S496–S499. [PubMed] [Google Scholar]
  33. Miyauchi T., Ishikawa T., Tomobe Y., Yanagisawa M., Kimura S., Sugishita Y., Ito I., Goto K., Masaki T. Characteristics of pressor response to endothelin in spontaneously hypertensive and Wistar-Kyoto rats. Hypertension. 1989 Oct;14(4):427–434. doi: 10.1161/01.hyp.14.4.427. [DOI] [PubMed] [Google Scholar]
  34. Nishimura M., Takahashi H., Matsusawa M., Ikegaki I., Sakamoto M., Nakanishi T., Hirabayashi M., Yoshimura M. Chronic intracerebroventricular infusions of endothelin elevate arterial pressure in rats. J Hypertens. 1991 Jan;9(1):71–76. doi: 10.1097/00004872-199101000-00011. [DOI] [PubMed] [Google Scholar]
  35. O'Brien E., Mee F., Atkins N., O'Malley K. Accuracy of the SpaceLabs 90207 determined by the British Hypertension Society protocol. J Hypertens. 1991 Jun;9(6):573–574. doi: 10.1097/00004872-199106000-00016. [DOI] [PubMed] [Google Scholar]
  36. Panza J. A., Casino P. R., Badar D. M., Quyyumi A. A. Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension. Circulation. 1993 May;87(5):1475–1481. doi: 10.1161/01.cir.87.5.1475. [DOI] [PubMed] [Google Scholar]
  37. Safar M. E., London G. M., Levenson J. A., Simon A. C., Chau N. P. Rapid dextran infusion in essential hypertension. Hypertension. 1979 Nov-Dec;1(6):615–623. doi: 10.1161/01.hyp.1.6.615. [DOI] [PubMed] [Google Scholar]
  38. Schiffrin E. L., Deng L. Y., Larochelle P. Blunted effects of endothelin upon small subcutaneous resistance arteries of mild essential hypertensive patients. J Hypertens. 1992 May;10(5):437–444. doi: 10.1097/00004872-199205000-00006. [DOI] [PubMed] [Google Scholar]
  39. Schiffrin E. L., Thibault G. Plasma endothelin in human essential hypertension. Am J Hypertens. 1991 Apr;4(4 Pt 1):303–308. doi: 10.1093/ajh/4.4.303. [DOI] [PubMed] [Google Scholar]
  40. Shichiri M., Hirata Y., Ando K., Emori T., Ohta K., Kimoto S., Ogura M., Inoue A., Marumo F. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension. 1990 May;15(5):493–496. doi: 10.1161/01.hyp.15.5.493. [DOI] [PubMed] [Google Scholar]
  41. Tomobe Y., Miyauchi T., Saito A., Yanagisawa M., Kimura S., Goto K., Masaki T. Effects of endothelin on the renal artery from spontaneously hypertensive and Wistar Kyoto rats. Eur J Pharmacol. 1988 Aug 2;152(3):373–374. doi: 10.1016/0014-2999(88)90736-4. [DOI] [PubMed] [Google Scholar]
  42. Vanhoutte P. M. Is endothelin involved in the pathogenesis of hypertension? Hypertension. 1993 Jun;21(6 Pt 1):747–751. doi: 10.1161/01.hyp.21.6.747. [DOI] [PubMed] [Google Scholar]
  43. Webb D. J., Haynes W. G. Endothelins come of age. Lancet. 1993 Dec 11;342(8885):1439–1440. doi: 10.1016/0140-6736(93)92928-m. [DOI] [PubMed] [Google Scholar]
  44. Wong-Dusting H. K., La M., Rand M. J. Mechanisms of the effects of endothelin on responses to noradrenaline and sympathetic nerve stimulation. Clin Exp Pharmacol Physiol. 1990 Apr;17(4):269–273. doi: 10.1111/j.1440-1681.1990.tb01319.x. [DOI] [PubMed] [Google Scholar]
  45. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  46. Yang Z. H., Richard V., von Segesser L., Bauer E., Stulz P., Turina M., Lüscher T. F. Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation. 1990 Jul;82(1):188–195. doi: 10.1161/01.cir.82.1.188. [DOI] [PubMed] [Google Scholar]
  47. Zelis R., Mason D. T. Comparison of the reflex reactivity of skin and muscle veins in the human forearm. J Clin Invest. 1969 Oct;48(10):1870–1877. doi: 10.1172/JCI106153. [DOI] [PMC free article] [PubMed] [Google Scholar]

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