(Hypertension. 1997;30:83-87.)
© 1997 American Heart Association, Inc.
Articles |
Clonidine and ST-91 May Activate Imidazoline Binding Sites in the Heart to Release Atrial Natriuretic Peptide
From the Laboratory of Cardiovascular Biochemistry, Research Center, Hotel-Dieu Hospital, Montreal, and Pharmacology Department, Faculty of Medicine, University of Montreal (C.L.) (Quebec, Canada).
Correspondence to Dr Jolanta Gutkowska, Laboratory of Cardiovascular Biochemistry, Centre de Recherche Hotel-Dieu de Montréal, 3850 St-Urbain St, Marie-de-la-Ferre Pavilion, Montreal, Quebec H2W 1T8, Canada. E-mail gutkowsj{at}ere.umontreal.ca
Abstract It is well established that the antihypertensive
drug clonidine acts through specific imidazoline receptors in the brain
and kidney to increase diuresis, natriuresis, and kaliuresis.
We have previously shown that the effects of clonidine are associated
with elevated plasma atrial natriuretic peptide (ANP).
Similar to clonidine, ST-91, a clonidine analogue that does not cross
the blood-brain barrier, evokes renal responses that are also
associated with elevated plasma ANP. The mechanisms of ANP increase
elicited by these imidazoline drugs are unclear. Since ANP is primarily
released from the cardiac atria, we investigated the direct effect of
the imidazoline drugs on ANP release by incubating left and right
atrial sections with 10-6 mol/L ST-91 in the
presence and absence of efaroxan, a selective imidazoline
I1 receptor antagonist, for 30 minutes at
37°C. ST-91 significantly stimulated ANP release, and the effect was
inhibited by 10-6 mol/L efaroxan. Further
studies using heart perfusion with the imidazoline drugs with and
without antagonists over 30 minutes revealed that both
clonidine and ST-91 gradually stimulated ANP release. Also, perfusion
with these compounds resulted in a gradual decrease in heart rate, but
bradycardia was significant only with clonidine. The effects of ST-91
were inhibited by 10-6 mol/L efaroxan and to a
lesser extent by 10-6 mol/L yohimbine,
implying that the actions of ST-91 were mainly mediated by
I1 receptors. On the other hand, the actions of clonidine
were inhibited by 10-5 mol/L efaroxan and by
10-6 mol/L yohimbine, an
2-adrenoceptor antagonist, which may suggest
that the actions of clonidine were preferentially mediated by
2-adrenoceptors in the heart. These results indicate
that the peripheral actions of clonidine are probably
mediated by 2 and imidazoline receptors and may involve
direct stimulation of ANP release by the cardiac atria—an effect that
may account for the increase in plasma ANP levels and diuresis
and natriuresis observed in vivo after administration of clonidine and
its analogues.
Key Words: imidazoles • clonidine • yohimbine • atrial natriuretic factor • receptors, adrenergic, alpha
This article has been cited by other articles:
 |
|
 |
|
  H. Guo, S. Takahashi, S. Cho, T. Hara, S. Tomiyasu, and K. Sumikawa The Effects of Dexmedetomidine on Left Ventricular Function During Hypoxia and Reoxygenation in Isolated Rat Hearts Anesth. Analg., March 1, 2005; 100(3): 629 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cao, C. W. Kang, S. Z. Kim, and S. H. Kim Augmentation of moxonidine-induced increase in ANP release by atrial hypertrophy Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H150 - H156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Raasch, B. Jungbluth, U. Schafer, W. Hauser, and P. Dominiak Modification of Noradrenaline Release in Pithed Spontaneously Hypertensive Rats by I1-Binding Sites in Addition to alpha 2-Adrenoceptors J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1063 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Schafer, C. Burgdorf, A. Engelhardt, T. Kurz, and G. Richardt Presynaptic Effects of Moxonidine in Isolated Buffer Perfused Rat Hearts: Role of Imidazoline-1 Receptors and alpha 2-Adrenoceptors J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Beaulieu and C. Lambert Peptidic regulation of heart rate and interactions with the autonomic nervous system Cardiovasc Res, March 1, 1998; 37(3): 578 - 585. [Abstract] [Full Text] [PDF]
|
|