Acetylcholine induces contraction in vergebral arteries from treated hypertensive patients.
Endothelium-dependent vasodilatation to acetylcholine is abnormal in animal models of hypertension. This abnormality reflects a change in the balance of relaxing and contracting factors produced in the vascular wall. In human cerebral arteries, endothelin has been implicated in the abnormal vasoconstrictor response following subarachnoid hemorrhage. This study tests the hypothesis that cerebral arteriolar dilatation to acetylcholine reduced in clinical hypertension due to an overproduction of endothelin. Our results show that at high concentrations of muscarinic agonist (0.3-3 microM), human vertebral arteries from hypertensive patients contract whereas those from normotensive patients remain maximally dilated. We conclude that the normal dilator response to acetylcholine is abrogated in vertebral arteries from treated hypertensive patients but endothelin-1 does not contribute to the abnormal responsiveness.
Charpie
J R
JR
Division of Pediatric Cardiology, University of Michigan Medical School Ann Arbor 48109-0622, USA.
Schreur
K D
KD
Papadopoulos
S M
SM
Webb
R C
RC
D000109:Acetylcholine / Q000494:pharmacology*; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D012189:Retrospective Studies; D012701:Serotonin / Q000494:pharmacology; D014711:Vertebral Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
D000959:Antihypertensive Agents; D019332:Endothelin-1; D018721:Muscarinic Agonists; D012701:Serotonin; D000109:Acetylcholine