[Effects of praeruptorin C on vascular hypertrophy, [Ca2+]i, collagen content and NO in renovascular and spontaneously hypertensive rats].
OBJECTIVE
To study the effects of praeruptorin C (pra-C), a pure constituent isolated from "Qian-Hu", the roots of Peucedanum praeruptorum Dunn. (Umbelliferae), on vascular hypertrophy, collagen content, transient [Ca2+]i, NO and vascular response of the thoracic aorta of renovascular and spontaneously hypertensive rats (RHR, SHR).


METHODS
RHR and SHR were given pra-C 20 mg.kg-1.d-1 for 9 weeks, ig. Blood pressure of both rats were measured using tail cuff manometry. Under inverted microscopy the length and width of the smooth muscle cells were measured by using computer software MICC (Dongnan University). [Ca2+]i of smooth muscle cell (SMCs) was measured with Fura-2/AM. By measuring the specific aminoacid hydroxyproline content, the collagen content was obtained. By using Griess reagent, the NO in the smooth muscle cells (SMCs) was measured.


RESULTS
The intermedia of the thoracic aorta in RHR was enlarged than that of the normal and pra-C groups. The size (length x width) of the SMCs of thoracic aorta from RHR increased 73.4 microns vs nomal 34.5 microns and pra-C 34 microns. The collagen content of thoracic aorta was 39% +/- 6.8% dry weight in RHR, they were 26.5% +/- 3% dry weight in normal and 25.6% +/- 1.1% dry weight in pra-C, RHR vs pra-C. The resting [Ca2+]i of single cell of SMCs was (62 +/- 6) nmol.L-1. In Hanks solution containing CaCl2 1 mmol.L-1, the resting [Ca2+]i of SMCs was (150 +/- 8) nmol.L-1 in normal. (226 +/- 11) nmol.L-1 in RHR. In presence of KCl 60 mmol.L-1, NE 10 mumol.L-1, ANG II 100 nmol.L-1 and ATP 30 mumol.L-1 the [Ca2+]i of SMCs were increased by 128%; 132%; 233% and 152% in RHR, respectively. The pra-C group was similar to the normal group. The resting [Ca2+]i of SMCs was (71 +/- 6) nmol.L-1 in control of SHR, in Hanks solution containing CaCl2 1 mmol.L-1. The resting [Ca2+]i of SMCs was (160 +/- 8) nmol.L-1 in normal, and (362 +/- 18) nmol.L-1 in SHR. In presence KCl 60 mmol.L-1 and NE 10 mumol.L-1 the [Ca2+]i of SMCs were increased by 235% and 200% in SHR, respectively. Pra-C group was similar to normal group. NO of SMCs was decreased 76% in SHR, pra-C group was nearly normal. The pra-C improved vascular responses of the thoracic aorta of RHR.


CONCLUSIONS
These results indicate that pra-C improved the vascular hypertrophy by decreasing the size of SMCs cells, collagen content. SMCs [Ca2+]i and increasing NO production.
Rao
M R
MR
Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China. rmr@990.net
Liu
W B
WB
Liu
P Q
PQ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003374:Coumarins / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D009569:Nitric Oxide; C058808:praeruptorin C; D003094:Collagen; D002118:Calcium