|
Correction
to
Lang et al.,
|
| |||||||||||||||||||||||||||||||||
-adrenergic effects of endogenous norepinephrine is therefore at least as likely an explanation of the findings as hyporesponsiveness to 
-adrenergic stimulation by isoproterenol. No mention is made of this possibility; a direct infusion of norepinephrine or phenylephrine would easily settle the issue. Second, since regional norepinephrine spillover is heavily dependent on blood flow, it would be important to provide information about nonadrenergically mediated increases in flow in order to interpret further the data on actual regional sympathetic activation. As in their previous report,2 the authors skirt this issue by referring to a study by Chang et al. regarding the "plasma appearance rate" for norepinephrine.3 This measure is derived from the calculation of regional spillover and has not been studied for a range of increases in blood flow such as those produced in these studies. Data from studies with another vasodilator, such as nitroprusside, would be helpful.
Finally, it seems that there is an error in the calculation of regional norepinephrine spillover. The standard formula multiplies, rather than divides, corrected venoarterial differences by regional plasma flow.
Steven R. Goldsmith, M.D.
Hennepin County Medical Center
Minneapolis, MN 55415
References
The dorsal-hand-vein technique, which provides a useful vasoactive model, was first described in 1981 by Aellig.2 An advantage of this technique is that one can use very small quantities of test substances, thus avoiding systemic reflexes. Lang and colleagues report a significant increase in the heart rate with the highest dose of isoproterenol. There was no such increase in the heart rate or blood pressure in our study. The hand-vein technique is reproducible and shows little day-to-day or diurnal variability.3 It has also been demonstrated that the local response to phenylephrine in the hand vein is correlated with the blood-pressure response to systemically infused phenylephrine.4 Although, as the authors explain, "the responsiveness of forearm resistance arteries is probably more important than that of dorsal hand veins in the regulation of peripheral vascular resistance," the results in veins are devoid of confounding factors, such as arterial-wall thickening and hypertrophy and hyperplasia of medial vascular smooth-muscle cells, which may be present in the arteries of persons with hypertension.
William Dachman, M.D.
Zoltan Vajo, M.D.
Haider Zafar, M.D.
Maricopa Medical Center
Phoenix, AZ 85008
References
2-adrenoceptor–mediated vasodilatation. It has repeatedly been demonstrated that sensitivity to salt is more prevalent in normotensive blacks than in whites.1 We wonder whether salt sensitivity was tested in the study population described by Lang et al. and whether the incidence of salt sensitivity was the same in the blacks and the whites.
We have reported disturbed adrenoceptor regulation in normotensive, salt-sensitive white subjects, with an enhanced up-regulation of the ratio of 2 to 2 adrenoceptors during high salt intake.2 Furthermore, we have reported a markedly reduced expression of 2 adrenoceptors in cultured fibroblasts from young, normotensive, salt-sensitive subjects, as compared with salt-resistant subjects.3 If these findings also apply to (presumably salt-sensitive) blacks, a reduced expression of 2 adrenoceptors would explain the findings of Lang et al. The expression of 2 adrenoceptors is probably mediated genetically, since their expression may be linked to different alleles of the human 2 adrenoceptor.4
We suggest that Lang et al. obtain fibroblast cultures to take the very interesting hemodynamic findings to the cellular level.
Peter Kotanko, M.D.
Falko Skrabal, M.D.
Karl Franzens University
A-8020 Graz, Austria
References
-2 and -2 adrenoceptors in salt-sensitive hypertension: an hypothesis. Life Sci 1989;45:2061-2076. [CrossRef][Medline]
2-Adrenoceptor density in fibroblast culture correlates with human NaCl sensitivity. Am J Physiol 1992;263:C623-C627. To the Editor: We are pleased that, using the dorsal-hand-vein technique, Dachman and his coworkers have confirmed our findings. We would be cautious, however, in accepting the advantages they claim for the hand-vein technique, particularly the lack of systemic effects. We have also used this technique extensively and have noted marked alterations in heart rate and blood pressure after the administration of doses of isoproterenol similar to those Dachman et al. used.1 Furthermore, hemodynamic measurements are relatively crude indicators of systemic effects, and we have shown that an increase in systemic norepinephrine spillover occurs after an intraarterial infusion of 60 ng of isoproterenol per minute — a dose that has no detectable hemodynamic effects.2
We share Kotanko and Skrabal's interest in salt sensitivity and whether it may be linked to the attenuated vasodilatation observed in blacks. In our study, sodium intake was standardized at 150 mmol per day to avoid alterations in the vascular response by extremes of sodium intake. In addition to Kotanko and Skrabal's studies with fibroblasts, the recent abstract by Svetkey and colleagues3 showing that an altered genotype at the 2-adrenergic–receptor locus is associated with hypertension in blacks but not in whites supports our finding of a racial difference in the vascular response to a 2-adrenoceptor agonist.
As we discussed in our article, an alteration in vascular responsiveness to sympathetic stimuli, such as either increased vasoconstriction mediated by -adrenergic receptors or decreased vasodilatation mediated by 2-adrenergic receptors, could contribute to overall alterations in vascular tone. Goldsmith raises the interesting possibility that -adrenergic hyperresponsiveness, mediated by the norepinephrine released by isoproterenol, may also have contributed to our findings. Although some, but not all, previous studies using systemic infusions of -adrenergic agonists support this hypothesis,4 these studies were flawed by the attendant problem of the production of systemic effects with baroreflex activation. When vascular effects have been studied more directly, decreased rather than increased responsiveness to phenylephrine has been observed in blacks.5 The issue of the effects of a wide range of increases in blood flow on local norepinephrine spillover is one that we are currently investigating. The strategy of using other vasodilators to increase the flow to the same extent as that seen with isoproterenol and then determining the norepinephrine spillover relies on the untested assumption that the other vasodilators have no effect on norepinephrine spillover other than that mediated through changes in flow.
We used the standard formula to calculate forearm norepinephrine spillover. A division sign was inadvertently substituted for the multiplication sign in the manuscript.
Chim C. Lang, M.D.
C. Michael Stein, M.D.
Alastair J.J. Wood, M.D.
Vanderbilt University School of Medicine
Nashville, TN 37232-6602
References
2-receptor agonist specifically desensitizes -receptor-mediated venodilation. Clin Pharmacol Ther 1993;54:187-193. [Medline]
-Adrenergic receptor-mediated release of norepinephrine in the human forearm. Clin Pharmacol Ther 1993;54:58-64.
- and -adrenergic receptor agonists: effects of race in borderline hypertensive compared to normotensive men. Am J Hypertens 1993;6:630-635. [Medline]
| |||||||||||||||||||||||||||||||||
This article has been cited by other articles:
HOME | SUBSCRIBE | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | PRIVACY | HELP | beta.nejm.org Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2008 Massachusetts Medical Society. All rights reserved. |
Previous
