The role of alpha adrenoceptor subtypes in sympathetic control of the acral-cutaneous microcirculation.
In pithed and anesthetized rats, laser-Doppler flowmetry was used to evaluate the role of alpha-1 and alpha-2 adrenoceptors in mediating sympathetic responses in acral regions of the cutaneous circulation. The intravenous administration of the selective alpha-1 agonist, phenylephrine, was a more potent vasopressor agent than BH-T 933 (a selective alpha-2 adrenoceptor agonist) in pithed rats. However, BH-T 933 was more potent and more efficacious than phenylephrine in reducing cutaneous microvascular perfusion (CP). BH-T 933 also caused a greater increase in cutaneous microvascular resistance. Neural and humoral sympathetic effects on CP were characterized with selective alpha-1 and alpha-2 adrenoceptor antagonists (prazosin and rauwolscine, respectively). It was found that frequency-related reductions in CP elicited by sciatic nerve stimulation were antagonized by prazosin, but not by rauwolscine. In fact, rauwolscine enhanced neurally evoked reductions in CP at the highest stimulation frequencies. However, both prazosin and rauwolscine antagonized reductions in CP elicited by electrical stimulation of the thoracolumbar outflow (sympathoadrenal activation). Ganglionic stimulation (intravenous 1,1-dimethyl-4-phenylpiperazinium) also caused a profound, transient reduction in CP that was abolished by rauwolscine, but was not significantly altered by prazosin. In contrast, 1,1-dimethyl-4-phenylpiperazinium-induced increases in mean arterial pressure were reduced by prazosin, but not by rauwolscine. In ketamine-anesthetized rats, rauwolscine caused a dose-related increase in CP without altering mean arterial pressure, whereas prazosin lowered mean arterial pressure but did not alter CP. We conclude that acral regions of the cutaneous vasculature are more sensitive to alpha-2 vis-a-vis alpha-1 adrenoceptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Willette
R N
RN
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Hieble
J P
JP
Sauermelch
C F
CF
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011928:Raynaud Disease / Q000503:physiopathology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013696:Temperature; D014655:Vascular Resistance / Q000187:drug effects
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C015603:azepexole