Vascular autonomy and its relation to the action of antihypertensive drugs

  • J. G. Collier


Raised peripheral resistance is a standard finding in patients with arterial hypertension and would account for the level of pressure at least in the chronic state. The mechanism for the increase in resistance remains obscure. Most theories have assumed that the vessels are constricted in response to disordered outside influences. Suggestions have included increased concentrations of the circulating constrictor substances adrenaline, noradrenaline, angiotensin II or the more recently described Na+-K+-ATPase inhibitor (de Wardener & MacGregor 1982). Alternatively increased levels of sympathetic nerve activity may be responsible, either because of some altered central mechanism, or because of altered peripheral control of mediator release (Brown & Macquin 1981). Some theories have considered that the abnormality may lie in the smooth muscle itself, and one popular hypothesis proposes that, at least in the chronic state, hypertension is maintained simply as a result of the physical bulk of the smooth muscle (Folkow 1978). Another hypothesis suggests that the smooth muscle has some specific abnormality of calcium handling (Robinson et al. 1982).


Plasma Renin Activity Plasma Renin Pulmonary Endothelial Cell Arachidonic Acid Derivative PGI2 Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Acker GM, Galen FX, Devaux C, Foote S, Papernik E, Pesty A, Menard J, Corval P (1982) Human chorionic cells in primary culture: a model for renin biosynthesis. J Clin Endocrinol Metab 55:902–909.PubMedCrossRefGoogle Scholar
  2. 2.
    Asaad MM, Antonaccio MJ (1982) Vascular wall renin in spontaneously hyptertensive rats. Hypertension 4:487–493.PubMedGoogle Scholar
  3. 3.
    Barrett JD, Eggena P, Sambhi MP (1978) Partial characterisation of aortic renin in the spontaneously hypertensive rat and its interrelationship with plasma renin, blood pressure and sodium balance. Clin Sci Molec Med 55:261–270.Google Scholar
  4. 4.
    Basso N, Lurnjek M, Tagnini AC (1977) Vascular renin-like activity and blood pressure. Mayo Clin Proc 52:437–441.PubMedGoogle Scholar
  5. 5.
    Biron P, Campeau L, David P (1969) Fate of angiotensin I and II in the human pulmonary circulation. Am J Cardiol 24:544–547.PubMedCrossRefGoogle Scholar
  6. 6.
    Brown MJ, Macquin I (1981) Is adrenaline the cause of essential hypertension? Lancet ii: 1079–1082.CrossRefGoogle Scholar
  7. 7.
    Busse R, Pohl U, Holtz J, Bassenge E (1983) Hypoxic dilation of coronary arteries in vitro mediated by endothelium. Blood Vessels 20:188.Google Scholar
  8. 8.
    Cocks TM, Angus JA (1983) Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305:627–630.PubMedCrossRefGoogle Scholar
  9. 9.
    Cohen RA, Shepherd JT, Vanhoutte PM (1983) Inhibitory role of endothelium in response of isolated canine coronary arteries to platelets. Blood Vessels 20:188–189.Google Scholar
  10. 10.
    Collier JG, Robinson BF (1974) Comparison of effects of locally infused angiotensin I and II on hand veins and forearm arteries in man: evidence for converting enzyme activity in limb vessels. Clin Sci Molec Med 47:189–192.Google Scholar
  11. 11.
    Collier JG, Robinson BF, Vane JR (1973) Reduction of pressor effects of angiotensin I in man by synthetic nonapeptide (B.P.P.9a or SQ 20,881) which inhibits converting enzyme. Lancet i: 72–79.CrossRefGoogle Scholar
  12. 12.
    Dengler H (1956) Über einen reinartigen Wirkstoff in Arterienextrakten. Naunyn-Schmiedenbergs Arch Exp Pathol Pharmakol 227:481–487.Google Scholar
  13. 13.
    de Wardener HE, MacGregor GA (1982) The natriuretic hormone and essential hypertension. Lancet i: 1450–1454.CrossRefGoogle Scholar
  14. 14.
    Donker AJM, Arisz L, Brentjens JRH, van der Hem GK, Hollemans HJG (1976) The effect of indomethacin on kidney function and plasma renin activity in man. Nephron 17:288–296.PubMedCrossRefGoogle Scholar
  15. 15.
    Doyle AE, Fraser JRE, Marshall RJ (1959) Reactivity of forearm vessels to vasoconstrictor substances in hypertensive and normotensive subjects. Clin Sci 18:441–454.PubMedGoogle Scholar
  16. 16.
    Eldor A, Falcone DJ, Hajjar DP, Minnick CR, Weksler BB (1981) Recovery of prostacyclin production by de-endothelialised rabbit aorta. Critical role of neo-intimal smooth muscle cells. J Clin Invest 67:735–741.PubMedCrossRefGoogle Scholar
  17. 17.
    Fitz Gerald GA, Brash AR, Falardeau P, Oates JA (1981) Estimated rate of prostacyclin secretion into the circulation of normal man. J Clin Invest 68:1271–1276.Google Scholar
  18. 18.
    Folkow B (1978) Cardiovascular structural adaptation; its role in the initiation and maintenance of primary hypertension. Clin Sci Mol Med 55 (Suppl 4):3s–22s.Google Scholar
  19. 19.
    Furchgott RF (1981) The requirement for endothelial cells in the relaxation of arteries by acetylcholine and some other vasodilators. TIPS July: 173–176.Google Scholar
  20. 20.
    Garst JB, Koletsky S, Wisenbaugh PE, Hadady M, Mathews D (1979) Arterial wall renin and renal venous renin in the hypertensive rat. Clin Sci Mol Med 56:41–46.Google Scholar
  21. 21.
    Gordon DB (1983) The role of renin substrate in hypertension. Hypertension 5:353–362.PubMedGoogle Scholar
  22. 22.
    Gould AB, Skeggs LT, Kahn JR (1964) The presence of renin activity in blood vessel walls. J Exp Med 119:389–399.PubMedCrossRefGoogle Scholar
  23. 23.
    Grose JH, Lebel M, Gbeassor FM (1980) Diminished urinary prostacyclin metabolite in essential hypertension. Clin Sci (Suppl 6) 59:121s–123s.PubMedGoogle Scholar
  24. 24.
    Gryglewski RJ, Bunting S, Moncade S, Flower RJ, Vane JR (1976) Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12:685–713.PubMedCrossRefGoogle Scholar
  25. 25.
    Haber E (1980) Specific inhibitors of renin. Clin Sci (Suppl 6) 59:7s–19s.PubMedGoogle Scholar
  26. 26.
    Hensby CN, Barnes PJ, Dollery CT, Dargie H (1979) Production of 6 oxo PGF by human lung in vivo. Lancet ii: 1162–1163.CrossRefGoogle Scholar
  27. 27.
    Herman AG, Moneada S, Vane JR (1977) Formation of prostacyclin (PGI2) by different layers of the arterial wall. Arch Int Pharmacodyn 227:162–163.PubMedGoogle Scholar
  28. 28.
    Hornych A, Safar M, Levenson J, Simon A, London G, Bariety J (1983) Proceedings of the Hypertension Congress, Milan. Abstract 190.Google Scholar
  29. 29.
    Johnson AR (1980) Human pulmonary endothelial cells in culture: activities of cells from arteries and cells from veins. J Clin Invest 65:841–850.PubMedCrossRefGoogle Scholar
  30. 30.
    Kilbom Å, Wennmalm A (1976) Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia. J Physiol 257:109–121.PubMedGoogle Scholar
  31. 31.
    Lopez-Overojo JA, Weber MA, Drayer JIM, Sealey JE, Laragh JH (1978) Effect of indomethacin alone and during diuretic or β-adrenoceptor blockade therapy on blood pressure and the renin system in essential hypertension. Clin Sci Molec Med 55 (Suppl 4):203s–205s.Google Scholar
  32. 32.
    MacGregor GA, Markandu ND, Roulston JE (1979). Does the renin-angiotensin system maintain blood pressure in both hypertensive and normotensive subjects? A comparison of propranolol, saralasin and Captopril. Clin Sci 57:145–148.Google Scholar
  33. 33.
    Manin’t Veld AJ, Schicht IM, Derkx FHM, De Bruyn JHB, Schalekamp MADH (1980) Effects of angiotensin converting enzyme inhibitor (Captopril) on blood pressure in anephric subjects. Br Med J 280:288–290.CrossRefGoogle Scholar
  34. 34.
    Meade TW, Imeson JD, Gordon D, Peart WS (1983) The epidemiology of plasma renin. Clin Sci 64:273–280.PubMedGoogle Scholar
  35. 35.
    Moneada S, Higgs EA, Evans JR (1977) Human arterial and venous tissues generate prostacyclin (prostaglandin X), a potent inhibitor of platelet aggregation. Lancet i: 18–20.Google Scholar
  36. 36.
    Moneada S, Korbut R, Bunting S, Vane JR (1978) Prostacyclin is a circulating hormone. Nature 273:767–768.CrossRefGoogle Scholar
  37. 37.
    Neri Serneri GG, Abbate R, Gensini GF, Panetta A, Casolo GC, Carini M (1983) TXA2 production by human arteries and veins. Prostaglandins 25:754–766.Google Scholar
  38. 38.
    Pace-Asciak CR, Carrara MC (1978) Evidence suggesting a systemic antihypertensive role for PGl2. Prostaglandins 15:704.Google Scholar
  39. 39.
    Piper PJ, Letts LG, Galton SA (1983) Generation of a leukotriene-like substance from porcine vascular and other tissues. Prostaglandins 25:591–599.PubMedCrossRefGoogle Scholar
  40. 40.
    Robinson BF, Collier JG, Dobbs RJ (1980) Acquired tolerance to dilator action of hydralazine during oral administration. Br J Clin Pharmacol 9:407–412.PubMedGoogle Scholar
  41. 41.
    Robinson BF, Dobbs RJ, Bayley S (1982) Response of forearm resistance vessels to verapamil and sodium nitroprusside in normotensive and hypertensive men: evidence for a functional abnormality in primary hypertension. Clin Sci 63:33–42.PubMedGoogle Scholar
  42. 42.
    Ryan JW, Ryan US (1977) Pulmonary endothelial cells. Fed Proc 36:2683–2691.PubMedGoogle Scholar
  43. 43.
    Sivertsson R (1970) The haemodynamic importance of structural vascular changes in essential hypertension. Acta Physiol Scand 343: whole issue.Google Scholar
  44. 44.
    Sparks HV, Belloni FL (1978) The peripheral circulation: local regulation. Ann Rev Physiol 40:67–92.CrossRefGoogle Scholar
  45. 45.
    Spokas EG, Folco G, Quilley J, Chander P, McGiff JC (1983) Endothelial mechanism in the vascular action of hydralazine. Hypertension 5:1 107–111.Google Scholar
  46. 46.
    Tewksbury DA, Dart RA (1982) High molecular weight angiotensinogen levels in hypertensive pregnant women. Hypertension 4:729–734.PubMedGoogle Scholar
  47. 47.
    Thurston H, Swales JD (1977) Blood pressure response of nephrectomised hypertensive rats to converting enzyme inhibition: evidence for persistent vascular renin activity. Clin Sci Molec Med 52:299–304.Google Scholar
  48. 48.
    Vane JR (1969) The release and fate of vasoactive hormones in the circulation. Br J Pharmac 35:209–242.Google Scholar
  49. 49.
    Verrechia C, Sercombe R, Seylaz J (1983) Endothelium removal enhances norepinephrine vasoconstriction. Blood Vessels 20:210.Google Scholar
  50. 50.
    Watkins J, Carl Abbott EC, Hensby CN, Webster J, Dollery CT (1980) Attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin. Br Med J 281:702–705.PubMedCrossRefGoogle Scholar
  51. 51.
    Wennmalm A (1978) Influence of indomethacin on the systemic and pulmonary vascular resistance in man. Clin Sci Molec Med 54:141–145.Google Scholar
  52. 52.
    Westfall TC (1977) Local regulation of adrenergic neurotransmission. Physiol Rev 57:659–727.PubMedGoogle Scholar
  53. 53.
    Williams TJ, Peck MJ (1977) Role of prostaglandin-mediated vasodilatation in inflammation. Nature 270:530–532.PubMedCrossRefGoogle Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag, GmbH & Co. KG, Darmstadt 1984

Authors and Affiliations

  • J. G. Collier
    • 1
  1. 1.Department of PharmacologySt George’s Hospital Medical SchoolLondonUK

Personalised recommendations