This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kooner, J. S. Articles by Mathias, C. J. Search for Related Content PubMed PubMed Citation Articles by Kooner, J. S. Articles by Mathias, C. J.

Circulation, Vol 84, 75-83, Copyright © 1991 by American Heart Association

ARTICLES

Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action

JS Kooner, R Birch, HL Frankel, WS Peart and CJ Mathias
Department of Medicine, St. Mary's Hospital, London, UK.

BACKGROUND. Clonidine, a partial presynaptic and postsynaptic alpha- adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated. METHODS AND RESULTS. The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors. CONCLUSIONS. Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension.

This article has been cited by other articles:

				A. Knaus, X. Zong, N. Beetz, R. Jahns, M. J. Lohse, M. Biel, and L. Hein Direct Inhibition of Cardiac Hyperpolarization-Activated Cyclic Nucleotide-Gated Pacemaker Channels by Clonidine Circulation, February 20, 2007; 115(7): 872 - 880. [Abstract] [Full Text] [PDF]

				J. Kimber, C. J. Mathias, A. J. Lees, K. Bleasdale-Barr, H. S. Chang, A. Churchyard, and L. Watson Physiological, pharmacological and neurohormonal assessment of autonomic function in progressive supranuclear palsy Brain, July 1, 2000; 123(7): 1422 - 1430. [Abstract] [Full Text] [PDF]

				E. R. Azevedo, G. E. Newton, and J. D. Parker Cardiac and systemic sympathetic activity in response to clonidine in human heart failure J. Am. Coll. Cardiol., January 1, 1999; 33(1): 186 - 191. [Abstract] [Full Text] [PDF]

				J. S. Kooner, C. N. May, S. Peart, and C. J. Mathias Separation of peripheral and central cardiovascular actions of angiotensin II Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2620 - H2626. [Abstract] [Full Text] [PDF]

				P. Ernsberger and M. A. Haxhiu The I1-imidazoline-binding site is a functional receptor mediating vasodepression via the ventral medulla Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1997; 273(5): R1572 - R1579. [Abstract] [Full Text] [PDF]

				C. C. Lang, C. M. Stein, R. A. Nelson, H. B. He, F. J. Belas, I. A. Blair, M. Wood, and A. J. J. Wood Sympathoinhibitory Response to Clonidine Is Blunted in Patients With Heart Failure Hypertension, September 1, 1997; 30(3): 392 - 397. [Abstract] [Full Text]

				C. C. Lang, C. M. Stein, H. B. He, F. J. Belas, I. A. Blair, M. Wood, and A. J. J. Wood Blunted Blood Pressure Response to Central Sympathoinhibition in Normotensive Blacks : Increased Importance of Nonsympathetic Factors in Blood Pressure Maintenance in Blacks Hypertension, August 1, 1997; 30(2): 157 - 162. [Abstract] [Full Text]

				M. M. El-Mas and A. A. Abdel-Rahman Role of Cardiac Output in Ethanol-Evoked Attenuation of Centrally Mediated Hypotension in Conscious Rats Hypertension, August 1, 1997; 30(2): 288 - 294. [Abstract] [Full Text]