title: Clonidine and a novel clonidine analog AL-12 cause sympathoinhibition in spontaneously hypertensive and diabetic spontaneously hypertensive rats.
abstract: This study examined the sympathoinhibitory effects of clonidine and a novel clonidine analog, AL-12, in rat models of genetic hypertension and a combined state of genetic hypertension and diabetes. Rats in the treatment groups were given either clonidine or AL-12 while the respective control groups received either saline or Tween 80 for 6 days. Physiological data were collected during this period, which was followed by acute studies on day 7 when bolus administrations (i.v.) of graded doses of noradrenaline, phenylephrine and methoxamine were carried out. It was observed that in AL-12-treated nondiabetic spontaneously hypertensive rats (SHR), the pressure responses to all adrenergic agonists were greater (p < 0.05) in the treated group, while in the diabetic SHR rats a larger pressure response was observed only to noradrenaline (p < 0.05). In nondiabetic SHR rats treated with clonidine, a greater (p < 0.05) pressure response was observed only in the case of phenylephrine. In the diabetic SHR rats treated with clonidine, the pressure responses to the adrenergic agonists were similar (p > 0.05) in the treated and its control animals except that methoxamine caused a greater (p < 0.05) pressure response in the control group. The data obtained suggest that clonidine and AL-12 act possibly via vascular alpha1 and alpha2 adrenoceptors present at both pre- and postsynaptic locations.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: M I A
authors.initials: MI
authors.lastname: Lazahari
authors.forename: M A
authors.initials: MA
authors.lastname: Sattar
authors.forename: N A
authors.initials: NA
authors.lastname: Abdullah
authors.forename: Md A H
authors.initials: MA
authors.lastname: Khan
authors.forename: E J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013311:Streptozocin
chemical_list: C532644:3,5-dichloro-4-(imidazolidin)-2-ylideneammonio benzoate dehydrate; D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D010656:Phenylephrine; D013311:Streptozocin; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine