Submitted on October 15, 2003
Accepted on February 18, 2004
AUGMENTATION OF MOXONIDINE-INDUCED INCREASE IN ANP RELEASE BY ATRIAL HYPERTROPHY
Chunhua Cao1, Chang Won Kang2, Sung Zoo Kim1, and Suhn Hee Kim1*
1 Department of Physiology, Chonbuk National University Medical School, Jeonju, Korea, Republic of
2 Department of Physiology, Chonbuk National University College of Veterinary Medicine, Jeonju, Korea, Republic of
* To whom correspondence should be addressed. E-mail: shkim{at}chonbuk.ac.kr.
Imidazoline receptors are divided into I1 and I2 subtypes. I1-imidazoline receptor is distributed in the heart and upregulated in hypertension or heart failure. The aim of this study was to define the possible role of I1-midazoline receptor in the regulation of atrial natriuretic peptide (ANP) release in hypertrophied atria. Experiments have been done in isolated perfused hypertrophied atria from remnant kidney hypertensive rats. Moxonidine, a relatively selective I1-imidazoline receptor agonist, caused a decrease in pulse pressure. Moxonidine (3, 10, 30 µmol/L) caused dose-dependent increases in ANP secretion, but clonidine (
2-adrenoceptor agonist) did not. The pretreatment with efaroxan (selective I1-imidazoline receptor antagonist) or rauwolscine (selective
2-adrenoceptor antagonist) inhibited moxonidine-induced increases in ANP secretion and interstitial ANP concentration and decrease in pulse pressure. However, the antagonistic effect of efaroxan on moxonidine-induced ANP secretion was greater than that of rauwolscine. Neither efaroxan nor rauwolscine itself has any significant effects on ANP secretion and pulse pressure. In hypertrophied atria, moxonidineinduced
increases in ANP secretion and decrease in pulse pressure were markedly augmented as compared with non-hypertrophied atria. The relative change in ANP secretion by moxonidine was positively correlated to atrial hypertrophy. The
accentuation by moxonidine of ANP secretion was attenuated by efaroxan but not by rauwolscine. These results show that moxonidine increases ANP release through preferentially the activation of atrial I1-imidazoline receptor with the different mechanisms from clonidine and this effect is augmented in hypertrophied atria. Therefore, we suggest that cardiac I1-imidazoline receptors play an important role in the regulation of blood pressure.
