Uptake-1 and cutaneous vascular sensitivity to norepinephrine in human hypertension

L. E. Dooley, D. H. Lu, Y. Liu, G. Stagni, M. J. Jamieson, A. M.M. Shepherd, D. L. Kellogg

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Vascular sensitivity to exogenous norepinephrine (NE) has been reported to be increased in hypertension. To elucidate the mechanism of this increase, we used bretylium tosylate (BT) to competitively inhibit pre-synaptic noradrenergic uptake-1. 11 hypertensive subjects (HTN), one week off anti-hypertensive medications, and 16 normotensives (NT) were studied. Subjects received 6 ascending doses of NE by iontophoresis (current*time: 100-24300 μA*sec) at each of 2 forearm skin sites. One site was pre-treated with iontophoretically applied BT; the second site served as a control. Skin blood flow at both sites was indexed by laser-Doppler flowmetry (LDF) during NE iontophoresis. Mean arterial pressure (MAP) was monitored continuously (Finapres) and cutaneous vascular conductance calculated (CVC=LDF/MAP). Dose response curves (DRC's, CVC vs. NE) were constructed. At the control site, the mean threshold NE dose was much lower (1027±713 μA*sec) in HTN than in NT (3750±1504 μA*sec). At the BT site the mean threshold NE dose was 227±73 μA*sec for HTN and was 125±17 μA*sec for NT. Thus, when uptake-1 function is intact vascular sensitivity to NE is greater in HTN than NT. Competitive inhibition of uptake-1 potentiates the vascular sensitivity to exogenous NE in both groups; however, this potentiation is greater in NT than in HTN so that NT are more sensitive to NE than HTN. These findings indicate that the effectiveness of pre-synaptic uptake-1 in clearing NE is reduced in HTN. (Supported by American Heart Assoc., Texas Affiliate).

Original languageEnglish (US)
Pages (from-to)68A
JournalJournal of Investigative Medicine
Issue number1
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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