This Article Full Text 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 Mukaddam-Daher, S. Articles by Gutkowska, J. Search for Related Content PubMed PubMed Citation Articles by Mukaddam-Daher, S. Articles by Gutkowska, J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines Hazardous Substances DB CLONIDINE

(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

Suhayla Mukaddam-Daher; Chantal Lambert; ; Jolanta Gutkowska

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]