Calcium utilization coupled to stimulation of postjunctional alpha-1 and alpha-2 adrenoceptors in isolated human resistance arteries.
Human s.c. resistance arteries (internal diameters 158-353 microns) were mounted in a microvascular myograph, and experiments were designed to examine the calcium pools utilized by selective stimulation of alpha-1 and alpha-2 adrenoceptors. In a concentration-dependent manner, phenylephrine and B-HT 933 evoked contractions mediated by alpha-1 and alpha-2 adrenoceptors, respectively, both in calcium-containing and in calcium-free saline. With respect to the maximum response to potassium in calcium-containing saline, the maximum responses to phenylephrine and B-HT 933 were 96 +/- 6 and 85 +/- 8%, respectively, in calcium-containing saline, and 79 +/- 4 and 14 +/- 2%, respectively, in calcium-free saline. A qualitatively similar difference in maximum responses to alpha-1 vs. alpha-2 adrenoceptor stimulation in calcium-free saline was demonstrated for norepinephrine in the presence of antagonists selective for the two alpha adrenoceptor subtypes. The maximum relaxation in calcium-containing saline produced by the calcium antagonist nitrendipine was 52 +/- 3% in vessels precontracted with phenylephrine, but 80 +/- 5% in vessels precontracted with B-HT 933. A quantitative difference in receptor reserves was demonstrated between alpha-1 and alpha-2 adrenoceptors; 90% of the maximum response was obtained at 34 +/- 5 and 57 +/- 8% receptor occupation, respectively. These data suggest that compared to responses mediated by stimulation of postjunctional alpha-1 adrenoceptors, stimulation of postjunctional alpha-2 adrenoceptors relies heavily on calcium influx. Stimulation of postjunctional alpha-2 adrenoceptors is, however, also coupled to intracellular release of calcium in isolated human s.c. resistance arteries.
Nielsen
H
H
Institute of Pharmacology & Danish Biomembrane Research Center, Aarhus.
Mortensen
F V
FV
Pilegaard
H K
HK
Hasenkam
J M
JM
Mulvany
M J
MJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009568:Nitrendipine; C015603:azepexole; D002118:Calcium; D009638:Norepinephrine