Solid dispersion of rutaecarpine improved its antihypertensive effect in spontaneously hypertensive rats.
It was reported previously that rutaecarpine produced a hypotensive effect in phenol-induced and 2-kidney, 1-clip hypertensive rats. However, the same dose of crude rutaecarpine did not produce significant hypotensive effects when applied to spontaneously hypertensive rats (SHR). In the present study, a different dose of rutaecarpine solid dispersion was administered intragastrically to SHR. The systolic blood pressure was monitored by the tail-cuff method with an electro-sphygmomanometer. The plasma concentration of rutaecarpine, calcitonin gene-related peptide (CGRP) and the mRNA levels of CGRP in dorsal root ganglion were determined. The results showed that administration of the solid dispersion significantly increased the blood concentration of rutaecarpine, accompanied by significant hypotensive effects in SHR in a dose-dependent manner. The levels of plasma CGRP were also elevated significantly, concomitantly with the increased mRNA levels in the dorsal root ganglion in a dose-dependent manner. It was concluded that a change of the dosage from the crude drug to solid dispersion could improve significantly the efficiency of rutaecarpine absorption and increase its plasma concentration. The anti-hypertensive effect exerted by rutaecarpine solid dispersion in SHR is mediated by CGRP.
Ding
Jin-Song
JS
Department of Pharmaceutics, School of Pharmaceutical Sciences, Central South University, No. 110 Xiang-Ya Road,Changsha, China.
Gao
Rui
R
Li
Dai
D
Peng
Jun
J
Ran
Li-Ling
LL
Li
Yuan-Jian
YJ
D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004304:Dosage Forms; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D026121:Indole Alkaloids / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D014665:Vasodilator Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D052999:Quinazolinones
D000959:Antihypertensive Agents; D015740:Calcitonin Gene-Related Peptide; D004304:Dosage Forms; D026121:Indole Alkaloids; D011799:Quinazolines; D012333:RNA, Messenger; D014665:Vasodilator Agents; C028632:rutecarpine; D052999:Quinazolinones