Chronic imidazoline receptor activation in spontaneously hypertensive rats.
BACKGROUND
Acute intravenous administration of moxonidine, an imidazoline I1-receptor agonist, reduces blood pressure (BP) in normotensive and hypertensive rats, induces diuresis and natriuresis, and stimulates plasma atrial natriuretic peptide (ANP). In these studies we investigated the involvement of natriuretic peptides (ANP and brain natriuretic peptide) in the effects of chronic activation of imidazoline receptors.


METHODS
Spontaneously hypertensive rats (SHR; 12 to 14 weeks old) received 7-day moxonidine treatment at various doses (10, 20, 60, and 120 microg/kg/h) via subcutaneously implanted osmotic minipumps.


RESULTS
Hemodynamic parameters (continuously monitored by telemetry) revealed that, compared with saline-treated rats, moxonidine dose-dependently decreased blood pressures (BPs). Maximal blood pressure lowering effect was achieved by day 4 of treatment, at which point 60 microg/kg/h reduced mean arterial pressure (MAP) by 14.5 +/- 6.8 mm Hg as compared with basal levels. The decrease in MAP was influenced by a drop in both diastolic and systolic pressures. Moxonidine treatment did not alter daily urinary sodium and potassium excretions, but 120 microg/kg/h moxonidine decreased urine volume after 2 days and increased cyclic guanosine 3'5'monophosphate excretion on days 4 to 7 of treatment. Chronic moxonidine treatment dose-dependently increased plasma ANP to reach, at 120 microg/kg/h, a 40% increase (P < .01) above that of corresponding saline-treated SHR, with a concomitant increase in left and right atrial ANP mRNA (more than twofold). Plasma BNP increased by 120 microg/kg/h moxonidine (11.0 +/- 1.1 v 16.5 +/- 1.9 pg/mL, P < .002) without significant increases in atrial and ventricular BNP mRNA.


CONCLUSIONS
ANP and BNP may be involved in the antihypertensive effect of chronic moxonidine treatment. Accordingly, natriuretic peptides may contribute to the sympatholytic and cardioprotective effects of chronic activation of imidazoline I1-receptors.
Menaouar
Ahmed
A
El-Ayoubi
Rouwayda
R
Jankowski
Marek
M
Gutkowska
Jolanta
J
Mukaddam-Daher
Suhayla
S
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000187:drug effects* / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D005260:Female; D015870:Gene Expression; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D020097:Natriuretic Peptide, Brain / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C043482:moxonidine