QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.067595v1 jpet.104.067595v2 310/2/446    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by El-Ayoubi, R. Articles by Mukaddam-Daher, S. Search for Related Content PubMed PubMed Citation Articles by El-Ayoubi, R. Articles by Mukaddam-Daher, S.

CARDIOVASCULAR

Imidazoline Receptors but Not ₂-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L'Université de Montréal Research Center, Campus Hotel-Dieu, Montréal, Quebec, Canada

We have recently identified imidazoline I₁-receptors in the heart. In the present study, we tested regulation of cardiac I₁-receptors versus ₂ -adrenoceptors in response to hypertension and to chronic exposure to agonist. Spontaneously hypertensive rats (SHR, 12–14 weeks old) received moxonidine (10, 60, and 120 µg/kg/h s.c.) for 1 and 4 weeks. Autoradiographic binding of ¹²⁵I-paraiodoclonidine (0.5 nM, 1 h, 22°C) and inhibition of binding with epinephrine (10^–10–10^–5 M) demonstrated the presence of ₂-adrenoceptors in heart atria and ventricles. Immunoblotting and reverse transcription-polymerase chain reaction identified _2A-_2B-, and _2C, and -adrenoceptor proteins and mRNA, respectively. However, compared with normotensive controls, cardiac ₂ -adrenoceptor kinetic parameters, receptor proteins, and mRNAs were not altered in SHR with or without moxonidine treatment. In contrast, autoradiography showed that up-regulated atrial I₁-receptors in SHR are dose-dependently normalized by 1 week, with no additional effect after 4 weeks of treatment. Moxonidine (120 µg/kg/h) decreased B_max in right (40.0 ± 2.9–7.0 ± 0.6 fmol/unit area; p < 0.01) and left (27.7 ± 2.8–7.1 ± 0.4 fmol/unit area; p < 0.01) atria, and decreased the 85- and 29-kDa imidazoline receptor protein bands, in right atria, to 51.8 ± 3.0% (p < 0.01) and 82.7 ± 5.2% (p < 0.03) of vehicle-treated SHR, respectively. Moxonidine-associated percentage of decrease in B_max only correlated with the 85-kDa protein (R² = 0.57; p < 0.006), suggesting that this protein may represent I₂-receptors. The weak but significant correlation between the two imidazoline receptor proteins (R² = 0.28; p < 0.03) implies that they arise from the same gene. In conclusion, the heart possesses I₁-receptors and ₂-adrenoceptors, but only I₁-receptors are responsive to hypertension and to chronic in vivo treatment with a selective I₁-receptor agonist.

Address correspondence to: Dr. Suhayla Mukaddam-Daher, Laboratory of Cardiovascular Biochemistry, CHUM Research Center, 3840 St-Urbain St. (6-816), Montréal, QC, Canada, H2W 1T8. E-mail: suhayla.mukaddamdaher{at}umontreal.ca