Impaired endothelium-dependent vasodilation in patients with essential hypertension: evidence that the abnormality is not at the muscarinic receptor level

J Am Coll Cardiol. 1994 Jun;23(7):1610-6. doi: 10.1016/0735-1097(94)90664-5.


Objectives: The purpose of this study was to determine whether the impaired endothelium-dependent vasodilation of hypertensive patients is related to a specific defect of the muscarinic receptor or to a broader abnormality of the vascular endothelium.

Background: Patients with essential hypertension have abnormal endothelium-dependent vasodilator response to acetylcholine. However, whether this results from an isolated dysfunction of the endothelial cell muscarinic receptor is unknown.

Methods: The responses of the forearm vasculature to acetylcholine and substance P (endothelium-dependent agents acting on different receptors) and to sodium nitroprusside (a direct dilator of vascular smooth muscle) were studied in eight hypertensive patients (six men, two women; mean age [+/- SD] 50 +/- 12 years) and eight normal control subjects (four men, four women; mean age 49 +/- 9 years). To determine the nitric oxide contribution to substance P-induced vasodilation, the vascular responses to substance P were also measured after inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain gauge plethysmography.

Results: The response to acetylcholine was significantly blunted in hypertensive patients (highest blood flow [mean +/- SD] 8.4 +/- 4 vs. 13.8 +/- 4 ml/min per 100 ml in control subjects, p < 0.03). Similarly, the vasodilator effect of substance P was significantly reduced in hypertensive patients (highest blood flow [mean +/- SD] 8.8 +/- 4 vs. 13.9 +/- 4 ml/min per 100 ml in control subjects, p < 0.03). A significant correlation was found between the maximal blood flow with acetylcholine and that with substance P (r = 0.68, p < 0.004). The vasodilator response to sodium nitroprusside was similar in patients and control subjects. The nitric oxide contribution to substance P-induced vasodilation was reduced in hypertensive patients, such that the responses to substance P measured during infusion of NG-monomethyl-L-arginine were not significantly different between the two groups.

Conclusions: These findings indicate that the endothelial abnormality of patients with essential hypertension is not restricted to the muscarinic cell receptor.

MeSH terms

  • Acetylcholine / pharmacology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Endothelium, Vascular / physiopathology*
  • Female
  • Forearm / blood supply
  • Humans
  • Hypertension / physiopathology*
  • Male
  • Middle Aged
  • Nitric Oxide / physiology
  • Nitroprusside / pharmacology
  • Receptors, Muscarinic / physiology*
  • Substance P / pharmacology
  • Vasodilation / physiology*
  • omega-N-Methylarginine


  • Receptors, Muscarinic
  • Nitroprusside
  • omega-N-Methylarginine
  • Nitric Oxide
  • Substance P
  • Arginine
  • Acetylcholine