Enhanced contraction to noradrenaline, serotonin and nerve stimulation but normal endothelium-derived relaxing factor response in skin small arteries in human primary hypertension.
1. We measured the reactivity of 2 mm long ring segments of human resistance arteries dissected from gluteal skin biopsies and mounted on wires in a Mulvany-Halpern myograph for recording isometric force. Arteries were taken from eight normotensive (N) volunteers (average age 46 years, blood pressure 126/82 mmHg) and eight untreated hypertensives (H; average age 48 years, blood pressure 149/101 mmHg). 2. In small diameter arteries (internal diameter less than 500 microns), the cumulative concentration-response curves to noradrenaline, serotonin and angiotensin II had a greater maximum by 72, 300 and 69%, respectively, in vessels from hypertensive patients than in those from normal volunteers. Nerve stimulation also caused a greater maximum contraction in hypertensive vessels (by 352%). 3. Arteries from H and N patients contracted submaximally by the thromboxane mimetic U46619 were similarly sensitive to the endothelium-dependent relaxing factor (EDRF) acetylcholine, indicating no difference in EDRF release or sensitivity. 4. Morphological measurements of the ratio of wall thickness to lumen radius of the wire-mounted vessels showed no significant difference between H and N vessels. 5. In larger arteries (internal diameter greater than 500 microns), no response to acetylcholine was noted in either H or N arteries. The sensitivity to serotonin and angiotensin II was similar between these arteries but the EC50 to noradrenaline was less in H than in N arteries (delta EC50 = 0.61 -log mol/L). 6. Subcutaneous resistance arteries with an internal diameter less than 500 microns from hypertensive patients show enhanced contractility to noradrenaline, serotonin and nerve stimulation despite a lack of detectable medial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Angus
J A
JA
Baker Medical Research Institute, Melbourne, Australia.
Jennings
G L
GL
Sudhir
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009213:Myography; D009569:Nitric Oxide / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D009638:Norepinephrine