Endothelium-dependent relaxation of small arteries from essential hypertensive patients: mechanisms and comparison with normotensive subjects and with responses of vessels from spontaneously hypertensive rats

Clin Sci (Lond). 1995 Jun;88(6):611-22. doi: 10.1042/cs0880611.


1. Impaired endothelium-dependent relaxation has been previously demonstrated in blood vessels of hypertensive rats and in humans with essential hypertension. Arteries from spontaneously hypertensive rats have been shown to produce, in response to high concentrations of acetylcholine, a vasoconstrictor substance called endothelium-derived contracting factor, the production of which can be inhibited by indomethacin or other cyclo-oxygenase inhibitors, suggesting that it is a prostanoid. The mechanisms involved in endothelium-dependent relaxation of human arteries are unclear, and the potential generation of endothelium-derived contracting factor by endothelium in human hypertension has not been established. 2. We investigated the effects of acetylcholine on precontracted small arteries dissected from gluteal subcutaneous fat biopsies from normotensive subjects and subjects with borderline and mild essential hypertension. Vessels from normotensive subjects and those from borderline hypertensive patients, precontracted by noradrenaline, were relaxed completely by acetylcholine, whereas those from patients with mild essential hypertension relaxed slightly but significantly less, indicating that generation of endothelium-derived relaxing factor (endothelium-derived nitric oxide) was only minimally reduced or that production of minor amounts of endothelium-derived contracting factor occurred in small arteries from these hypertensive subjects. This impairment of endothelium-dependent relaxation was not corrected by indomethacin, which indicated that the contribution of endothelium-derived contracting factor, if any, was minimal in this subset of essential hypertensive patients. In contrast, mesenteric small arteries of adult spontaneously hypertensive rats presented strong contractions in response to the higher concentrations of acetylcholine, which were abolished by exposure to indomethacin. 3. The relaxation induced by acetylcholine in arteries from both hypertensive and normotensive humans was partially blunted (by 30%) by pretreatment with 0.1 mmol/l NG-nitro-L-arginine methyl ester or NG-nitro-monomethyl-L-arginine (inhibitors of nitric oxide synthase) and by 10 mumol/l Methylene Blue (a blocker of soluble guanylate cyclase), indicating the role of endothelium-derived nitric oxide and the generation of its intracellular second messenger cyclic guanosine monophosphate in acetylcholine-induced relaxation. The remaining relaxation elicited by acetylcholine could be blocked with 30 mmol/l KCl or with 10 mumol/l ouabain (inhibitor of Na+, K(+)-ATPase), and, when combined with NG-nitro-L-arginine methyl ester, these interventions abolished acetylcholine-induced relaxation. Tolbutamide at 2 mmol/l or 10 mumol/l glyburide (blockers of ATP-sensitive potassium channels) partially inhibited NG-nitro-L-arginine methyl ester-resistant endothelium-dependent relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Adult
  • Animals
  • Apamin / pharmacology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Arterioles / drug effects
  • Arterioles / physiology
  • Charybdotoxin
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology*
  • Humans
  • Hypertension / physiopathology*
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Male
  • Methylene Blue / pharmacology
  • Middle Aged
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / biosynthesis*
  • Ouabain / pharmacology
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Scorpion Venoms / pharmacology
  • Tolbutamide / pharmacology
  • Vasoconstriction / drug effects*
  • omega-N-Methylarginine


  • Scorpion Venoms
  • Charybdotoxin
  • Apamin
  • omega-N-Methylarginine
  • Nitric Oxide
  • Ouabain
  • Potassium Chloride
  • Arginine
  • Tolbutamide
  • Acetylcholine
  • Methylene Blue
  • NG-Nitroarginine Methyl Ester
  • Indomethacin