(Circulation. 1998;97:1873-1874.)
© 1998 American Heart Association, Inc.
Angiotensin II and Coronary Sympathetic Vasodilation
Kenneth M. Kessler, MD
Division of Cardiology,
University of Miami School of Medicine
Rhonda M. Kessler, MD
Miami Children's Hospital,
Miami, Fla
To the Editor:
Saino et al1 and Lyons et
al2 published provocative findings
regarding the vascular level interaction of the sympathetic and
renin-angiotensin systems. Both authors present
possible mechanisms for their observations based on literature evidence
and their own observations of the ability of angiotensin to
enhance sympathetically mediated vasoconstriction. In addition to the
possibilities they presented we would like to suggest that
there is the potential that the enhanced vasoconstriction is being
mediated by angiotensin per se, which in the presence of
catecholamines is being transformed from a subpressor to
pressor effect.3 4 Such a possibility is
consistent with the inhibition of the interaction noted in the
presence of perindoprilat.2 We would appreciate
the thoughts and any observations the authors have with respect to such
a possibility.
References
1.
Saino A, Pomidossi G, Perondi R, Valentini R, Rimini A, Di
Francesco L, Mancia G. Intracoronary angiotensin II
potentiates coronary sympathetic vasoconstriction in humans.
Circulation. 1997;96:148–153.[Abstract/Free Full Text]
2.
Lyons D, Roy S, O'Byrne S, Swift CG. ACE inhibition:
postsynaptic adrenergic sympatholytic action in men.
Circulation. 1997;96:911–915.[Abstract/Free Full Text]
3.
Kessler K, Harakal C. Potentiation of the vasoconstrictor
effect of angiotensin by catecholamines in
vitro. Fed Proc. 1967;26:465. Abstract.
4.
Kessler RK, Kessler KM, Harakal C. Potentiation of
angiotensin by catecholamines: structure
activity relationships. Fed Proc. 1968;27:712. Abstract.
Response
Dr Antonio Saino;
; Prof Giuseppe Mancia
Cattedra di Medicina Interna,
University of Milan,
Ospedale S Gerardo,
Dei TinTori,
Monza (Milano), Italy
There is no question that angiotensin II can play
its enhancing effects on the sympathetic nervous system at various
levels and that not only a presynaptic potentiation of
norepinephrine secretion but also an amplification of the
responsiveness of adrenergic receptors to neural stimuli is involved as
indicated by the data of Lyons et al.1 In a study
we performed several years ago in humans,2 we
also suggested this to be the case because in hypertensive patients
both acute and long-term ACE inhibition attenuated the reflex increase
in forearm vascular resistance due to unloading of cardiac receptors
without any concomitant alteration of the reflex increase in plasma
norepinephrine.
There is also no question that the enhancing effect of
angiotensin II on sympathetic
cardiovascular influences is reciprocated because
sympathetic nerve activity is an important determinant of renal
secretion of renin3 4 and thus of the activity of
the renin-angiotensin system. It is certainly possible, on
the basis of the in vitro findings of Kessler et
al,5 that this activity is increased by
sympathetic influences also because of an enhanced effect of
angiotensin II on its receptors. It would be important,
however, to device a way to see whether this is the case also in vivo
and what is the relative importance of this mechanism in the overall
positive feed-back interaction between the sympathetic and the
renin-angiotensin systems.
References
1.
Lyons D, Roy S, O'Byrne S, Swift CG. ACE inhibition:
postsynaptic adrenergic sympatholytic action in men.
Circulation. 1997;96:911–915.
2.
Morganti A, Grassi G, Giannattasio C, Bolla G, Turolo L, Saino
A, Sala C, Mancia G, Zanchetti A. Effect of angiotensin
converting enzyme inhibition on cardiovascular
regulation during reflex sympathetic activation in sodium replete
patients with essential hypertension. J Hypertens. 1989;7:825–835.[Medline]
[Order article via Infotrieve]
3.
Mancia G, Romero JC, Shepherd JT. Continuous inhibition of
renin release in dogs by vagally innervated receptors in
the cardiopulmonary region. Circ Res. 1975;36:529–535.[Abstract/Free Full Text]
4.
Grassi G, Giannattasio C, Saino A, Sabadini E, Capozi A,
Sampieri L, Cuspidi C, Mancia G. Cardiopulmonary receptor
modulation of plasma renin activity in normotensive and hypertensive
subjects. Hypertension. 1988;11:92–99.[Abstract/Free Full Text]
5.
Kessler K, Harakal C. Potentiation of vasoconstrictor effect of
angiotensin by catecholamines in vitro.
Fed Proc. 1968;27:712.
Response
Declan Lyons, MSc, MRCP, MD
King's College School of Medicine,
London, UK
Drs Kessler and Kessler suggest that the vasoconstricting effect
of angiotensin II may be enhanced by sympathetically
mediated vasoconstriction. The suggestion is that higher local
concentrations of either angiotensin II or perindoprilat
are achieved when a vessel is noradrenergically
preconstricted by infused norepinephrine or lower body
negative pressure. However, the dose of perindoprilat used in our study
was not, as suggested by Drs Kessler and Kessler, converted from a
subpressor to pressor dose by noradrenergic
preconstriction as perindoprilat (5 nmol/mL) virtually abolishes the
vasoconstricting action of angiotensin I (200 pmol/min)
when coinfused at the brachial artery (unpublished data), though it has
no effect on basal forearm blood flow.R1
Finally, submaximal noradrenergic preconstriction of a
blood vessel is likely to attenuate the vasoconstricting potential of
any coinfused vasoconstrictor and thus offset, at least in part, the
effect of a local increase in concentration produced by
preconstriction.
References
R1.
Lyons D, Roy S, O'Byrne S, Swift CG. ACE
inhibition: postsynaptic adrenergic sympatholytic action in
men. Circulation. 1997;96:911–915.
