Response to Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans
Given the dominant effect of the autonomic nervous system in counteracting alterations in cardiovascular function, we are not surprised that Schlaich and Schmieder1 were unable to show significant changes in renal plasma flow during systemic administration of NO synthase inhibitors, hence our effort to eliminate this confounding factor by inducing autonomic withdrawal with the ganglionic blocker trimethaphan. This approach allowed us to unmask the substantial role that NO has on blood pressure regulation2 and the role that the autonomic nervous system plays in the increase in blood pressure associated with obesity.3 It is possible, as suggested by Schlaich and Schmieder,1 that a similar experimental approach may help us define the role of other mechanisms, like oxidative stress, if effective and selective inhibitors of this process can be given during ganglionic blockade.
We recognize that the relative importance of the autonomic nervous system or any of these other factors will vary with the conditions of study (eg, supine versus upright posture, low versus high salt intake, etc) and the underlying disease (eg, obesity-associated hypertension, renovascular hypertension, etc). The conclusions of our study, therefore, can only be applied to the regulation of blood pressure in normal subjects in the supine position, as stated in our article. It is also important to recognize that this reductionist approach, as useful as we obviously believe it is, will not allow us to study the interactions that exist among the autonomic nervous system, the renin–angiotensin system, oxidative stress, and NO pathways, interactions that also play a role in the regulation of blood pressure. Neither does our approach allow us to evaluate the long-term effects of these factors on blood pressure (eg, vascular remodeling).
Despite its inherent limitations, we are pleased that Schlaich and Schmieder1 found our work of at least some value in exploring the role of the autonomic nervous system and NO pathways to blood pressure regulation and the potential of applying a similar approach to improve our understanding of hypertension.
Schlaich MP, Schmieder RE. Contribution of endothelial nitric oxide to blood pressure in humans. Hypertension. 2007; 49: e29.
Gamboa A, Shibao C, Diedrich A, Choi L, Pohar B, Jordan J, Paranjape S, Farley G, Biaggioni I. Contribution of endothelial nitric oxide to blood pressure in humans. Hypertension. 2007; 49: 170–177.
Shibao C, Gamboa A, Diedrich A, Ertl AC, Chen KY, Byrne DW, Farley G, Paranjape SY, Davis SN, Biaggioni I. Autonomic contribution to blood pressure and metabolism in obesity. Hypertension. 2007; 49: 27–33.