Acute and chronic sympathoinhibition on carotid artery diameter of spontaneously hypertensive rats: effects of clonidine and flesinoxan.
1. Hypertensive conduit arteries are thicker and stiffer than those of normotensive controls. Whether they are specifically sensitive to central sympathoinhibition has never been investigated. 2. The effects of acute (24 h infusion) and chronic (4 week infusion) treatments with clonidine (0.01 and 0.1 mg/kg per day) and flesinoxan (1 and 3 mg/kg per day) on carotid artery diameter were investigated in spontaneously hypertensive rats. At the end of treatment, blood pressure (BP) was recorded in the rats while they were conscious. Rats were then anaesthetized for carotid artery diameter measurements using an ultrasonic echotracking device. 3. In conscious rats, clonidine significantly decreased BP and heart rate (HR) following acute but not chronic treatment. In contrast, flesinoxan significantly decreased BP following both the acute and chronic treatment. In anaesthetized animals, the two agents have opposite effects on isobaric carotid artery diameter, with a decrease under clonidine and an increase under flesinoxan. After 4 weeks infusion, the reactivity of aortic rings was studied in organ chambers. Flesinoxan, but not clonidine, caused the relaxation of potassium chloride precontracted aortic segments. 4. The results indicate that although clonidine and flesinoxan are centrally acting antihypertensive agents, the drug-induced changes in isobaric carotid diameter may be influenced by local factors independent of the central action of the two drugs.
Dabiré
H
H
Institut National de la Santé et de la Recherche Médicale U337, Paris, France.
Chamiot-Clerc
P
P
Chaouche-Teyara
K
K
Fournier
B
B
Safar
M E
ME
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology; D003000:Clonidine / Q000494:pharmacology*; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; C056895:flesinoxan; D011189:Potassium Chloride; D003000:Clonidine; D009638:Norepinephrine