Cardiac effects of moxonidine in spontaneously hypertensive obese rats.
Moxonidine, an imidazoline receptor agonist that acts centrally to inhibit sympathetic activity, has been shown to reduce effectively blood pressure, fasting insulin levels, and free fatty acids. In this study, we investigated the long-term effects of moxonidine treatment on cardiac natriuretic peptides (ANP and BNP) in Spontaneously Hypertensive Obese Rats (SHROBs), a rat model that resembles human Syndrome X. SHROBs expressing spontaneous hypertension, insulin resistance, and genetic obesity (weight 590 +/- 20 g, at 30 weeks) received moxonidine in chow at 4 mg/kg/day for 15 days. Moxonidine significantly reduced not only systolic blood pressure (187 +/- 6 versus 156 +/- 5 mm Hg, P < 0.05) but also plasma ANP (1595 +/- 371 versus 793 +/- 131 pg/mL, P < 0.05) and BNP (22 +/- 3 versus 14 +/- 1 pg/mL, P < 0.04), without influencing cardiac content of either peptide. Semi-quantitative PCR revealed that atrial ANPmRNA/GAPDHmRNA decreased to 39% 6 10% of pair-fed controls, P < 0.03. In left ventricles, moxonidine also decreased ANP mRNA to 69% +/- 7% and BNP mRNA to 74% +/- 6% of control, P < 0.02, but right ventricular ANP and BNP mRNA were not affected. These findings indicate that chronic inhibition of sympathetic activity with moxonidine in SHROB is associated with decreased ventricular natriuretic peptide transcription, consistent with the cardioprotective effects of moxonidine given the role of ANP and BNP as markers of cadiac disease. Moxonidine also improves the metabolic profile in these rats, thus it may be considered the drug of choice in treatment of metabolic syndrome X.
Mukaddam-Daher
S
S
CHUM-Research Center, Universite de Montreal, Montreal, QC, Canada. suhayla.mukaddam-daher@umontreal.ca
Menaouar
A
A
El-Ayoubi
R
R
Gutkowska
J
J
Jankowski
M
M
Velliquette
R A
RA
Ernsberger
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D007093:Imidazoles; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C043482:moxonidine