Size and site-dependent heterogeneity of human vascular responses in vitro.
Ring segments of splanchnic, peripheral, coronary, pulmonary and uterine conduit arteries obtained during surgery were studied in tissue baths. Resistance arteries dissected from various sites were studied in a myograph. Both conduit and resistance vessels contracted in response to the alpha 1-agonist phenylephrine (10(-7) to 10(-4) mol/l), an effect that was antagonized by the alpha 1-antagonist doxazosin (10(-8) to 10(-6) mol/l). However, the alpha 2-agonists BHT 933 (10(-7) to 10(-4) mol/l) and UK 14304 (10(-7) to 10(-4) mol/l) only contracted the resistance vessels and not the conduit arteries. The response to BHT 933 was competitively antagonized by the alpha 2-antagonist yohimbine (3.10(-8) to 3.10(-7) mol/l) and the magnitude of the contractile response was inversely related to vessel size. Similarly, neuropeptide Y (10(-9) to 10(-6) mol/l) contracted only the resistance vessels, and induced marked tachyphylaxis. Atrial natriuretic peptide (ANP; 10(-8) to 10(-6) mol/l) produced concentration-dependent relaxation in all conduit arteries studied, being ineffective in resistance arteries from subcutaneous or omental sites, but relaxed those from renal tissue and skeletal muscle. Calcitonin gene-related peptide (10(-8) to 10(-6) mol/l) and vasoactive intestinal peptide (10(-9) to 10(-6) mol/l) relaxed both conduit and resistance arteries. This response was dependent on the integrity of the endothelium in the systemic conduit but not the resistance vessels. These results indicate that the receptors for adrenergic agonists and vasoactive peptides are varyingly distributed throughout the human vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
Hughes
A D
AD
Department of Clinical Pharmacology, St Mary's Hospital, London.
Thom
S A
SA
Martin
G N
GN
Nielsen
H
H
Hair
W M
WM
Schachter
M
M
Sever
P S
PS
D001158:Arteries / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D015740:Calcitonin Gene-Related Peptide; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D001381:Azepines; D009478:Neuropeptide Y; D009479:Neuropeptides; D011810:Quinoxalines; D010656:Phenylephrine; D014660:Vasoactive Intestinal Peptide; D000068438:Brimonidine Tartrate; D009320:Atrial Natriuretic Factor; C015603:azepexole; D015740:Calcitonin Gene-Related Peptide