Effects of clonidine and flesinoxan on blood pressure variability in conscious spontaneously hypertensive rats.
The effects of two centrally acting antihypertensive agents, clonidine (0.1 mg/kg/day s.c.) and flesinoxan (1 mg/kg/day s.c.), on short-term blood pressure variability (BPV) were investigated in conscious spontaneously hypertensive rats (SHRs). The drugs were infused subcutaneously during 24 h and 4 weeks by osmotic minipumps. BPV was characterized by spectral analysis. In conscious SHRs, clonidine significantly and preferentially reduced the low frequency (LF; 0.25-0.75 Hz) oscillations of mean arterial pressure (MAP) in short-term (24 h) and long-term (4 weeks) treatments but significantly decreased MAP level only in short-term treatments. In contrast, flesinoxan significantly reduced MAP level whatever the duration of infusion but decreased LF-MAP only in short-term treatments. These results show that centrally mediated inhibition of sympathetic tone by stimulation of either alpha2-adrenoceptors or 5-HT1A (serotonin) receptors can reduce BPV. This effect is independent of the modifications in BP level. The effects of the drugs on baroreceptors may also contribute to the decrease in BPV. The dual properties of clonidine (alpha2-adrenoceptors and imidazoline receptors) may account for its differential effects on BP level and BPV.
Chaouche-Teyara
K
K
INSERM U 337, Paris, France.
Lacolley
P
P
Challande
P
P
Fournier
B
B
Laurent
S
S
Safar
M
M
Dabiré
H
H
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D054755:Imidazoline Receptors; D007279:Injections, Subcutaneous; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011955:Receptors, Drug / Q000819:agonists; D013997:Time Factors
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D054755:Imidazoline Receptors; D010879:Piperazines; D011955:Receptors, Drug; C056895:flesinoxan; D003000:Clonidine