Response to Possible Difference in the Sympathetic Activation on Extreme Dippers With or Without Exaggerated Morning Surge
We appreciate the interest of Yano and Kario1 in our study documenting the neuroadrenergic abnormalities characterizing different nighttime ambulatory blood pressure (BP) profiles. In their letter, the authors make 2 major points. First, they underline that our findings support the data that they collected throughout α-blocker administration in reverse dippers.2 Second, they disagree with the lack of “correlation between extreme dipper status and morning sympathetic activation” inferred from our data.
As far as the first comment is concerned, we are pleased that the authors share our thinking on this issue. However, we would like to emphasize that our microneurographic evidence provides direct demonstration of the adrenergic overdrive seen in extreme dippers, which was indirectly inferred in the study by Kario et al3 by the finding of a potentiated BP fall in response to doxazosin administration. We emphasize that information obtained by indirect approaches assessing sympathetic function has not always been confirmed by direct techniques in the past. A typical example is represented by the data showing that α-blockade may attenuate the BP response to acute cigarette smoking,4 a finding suggesting the occurrence of an adrenergic overdrive during smoking. However, microneurographic nerve recordings have shown that central sympathetic outflow is inhibited during smoking and that only peripheral secretion of norepinephrine (on which α-blockade may act) is increased.5
The second point made by Yano and Kario1 refers to the fact that, in our study, no correlation between extreme dipping status and sympathetic activation at awakening has been found. We emphasize, however, that our study was not designed to determine the behavior of sympathetic drive in the early morning hours. Indeed, we assessed sympathetic activity in an experimental session performed between 9 to 9:30 am and 11 to 11:30 am. This certainly cannot be regarded as the period of the morning BP surge, which usually begins at awakening well before 9 am. Thus, our data cannot help us to determine whether and to what extent the sympathetic activation occurring during awakening is related to the dipping status. We emphasize that the issue is of extreme scientific and clinical interest, and we actually started a study a few months ago aimed at answering this question and, in general, at clarifying the neuroadrenergic component of the morning BP surge. Finally, we fully agree with the comment that the behavior of the BP and sympathetic response to the dipping or nondipping phenomenon may be affected by aging, which, indeed, profoundly alters not only sympathetic function during sleep but also adrenergic responses to a variety of physiological stimuli.6
Yano Y, Kario K. Possible difference in the sympathetic activation on extreme dippers with or without exaggerated morning surge. Hypertension. 2009; 53: e1.
Grassi G, Seravalle G, Quarti-Trevano F, Dell'Oro R, Bombelli M, Cuspidi C, Facchetti R, Bolla G, Mancia G. Adrenergic, metabolic, and reflex abnormalities in reverse and extreme dipper hypertensives. Hypertension. 2008; 52: 925–931.
Kario K, Schwartz JE, Pickering TG. Changes of nocturnal blood pressure dipping status in hypertensives by nighttime dosing of alpha-adrenergic blocker, doxazosin: results from the HALT study. Hypertension. 2000; 35: 787–794.
Groppelli A, Omboni S, Parati G, Mancia G. Blood pressure and heart rate response to repeated smoking before and after beta-blockade and selective alpha 1 inhibition. J Hypertens. 1990; 8 (suppl): S35–S40.
Grassi G, Seravalle G, Calhoun DA, Bolla GB, Giannattasio C, Marabini M, Del Bo A, Mancia G. Mechanisms responsible for sympathetic activation by cigarette smoking in humans. Circulation. 1994; 90: 248–253.
Grassi G, Seravalle G, Turri C, Bertinieri G, Dell'Oro R, Mancia G. Impairment of thermoregulatory control of skin sympathetic nerve traffic in the elderly. Circulation. 2003; 108: 729–735.