Methods for measuring vascular and nonvascular alpha-receptor sensitivity in humans.
Since increased alpha-adrenergic reactivity may participate in the pathophysiology of essential hypertension, methods for accurately assessing in vivo alpha-receptor sensitivity in humans might be useful. The goals of this study were to employ previously used methods, namely pupillometry and local forearm intraarterial infusions, to assess alpha-receptor sensitivity, create an in vivo environment of decreased sympathetic drive (plasma norepinephrine) and increased alpha-receptor number (platelet alpha 2), in which increased alpha-receptor sensitivity to exogenous agonists might occur. Five patients with minimally elevated blood pressure (139 +/- 5/90 +/- 4 mm Hg) while on diuretic monotherapy completed assessment of biochemical and physiologic variables on diuretic alone and again on diuretic and guanadrel. Guanadrel plus diuretic compared with diuretic alone lowered the seated diastolic and standing systolic and diastolic blood pressure. Heart rate was decreased about 10 beats/min. Baseline supine norepinephrine was reduced an average of 40% (from 281 +/- 23 to 168 +/- 16 pg/ml, p = 0.03), and platelet alpha 2-receptors were increased roughly 40% (from 178 +/- 34 to 250 +/- 54 fmol/micrograms, p = 0.07). Despite the expected decrease in sympathetic drive and increase in alpha-receptors (platelet alpha 2), the pupillary mydriatic response to phenylephrine and the forearm vasoconstrictor response to intraarterial norepinephrine were not augmented. The failure to detect increased physiologic responsiveness in the presence of decreased norepinephrine and increased alpha 2-receptor number lends itself to multiple explanations which need to be tested in future research.(ABSTRACT TRUNCATED AT 250 WORDS)
B
B
Egan
R
R
Neubig
R H
RH
Schneider
S
S
Julius
D001132:Arm / Q000098:blood supply; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014666:Vasomotor System / Q000502:physiology*
D006146:Guanidines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C004945:guanadrel