praeruptorin-c and Hypertension--Renovascular

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).. 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.. 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.. 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.

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Calcium; Calcium Channel Blockers; Cells, Cultured; Collagen; Coumarins; Drugs, Chinese Herbal; Hypertension; Hypertension, Renovascular; Hypertrophy; Muscle, Smooth, Vascular; Nitric Oxide; Random Allocation; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley

To study the intracellular free calcium ([Ca2+]i) in normal and hypertrophic left ventricular myocytes isolated from adult rat hearts and the effects of praeruptorine C (Pra-C) on them.. [Ca2+]i of single myocyte was measured with Fura 2-AM.. The resting [Ca2+]i was 87 +/- 4 nmol.L-1 in normal left ventricular myocytes, 123 +/- 7 nmol.L-1 in hypertrophied myocytes. After exposure to KCl (20, 40, and 60 mmol.L-1), the [Ca2+]i were increased by 66%, 141%, and 268% in normal myocytes, and 77%, 185%, and 243% in hypertrophic myocytes, respectively. Pra-C (1, 10, and 100 mumol.L-1) concentration-dependently inhibited the [Ca2+]i elevation caused by KCl (35 mmol.L-1) or norepinephrine (20 mumol.L-1) in both normal and hypertrophied myocytes. All of the effects of Pra-C were similar to that of nifedipine.. [Ca2+]i of hypertrophied myocytes was higher than that of normal ones and Pra-C decrease the [Ca2+]i elevation in left ventricular myocytes resulted from its calcium channel blockade.

Topics: Animals; Butyrates; Calcium; Calcium Channel Blockers; Coumarins; Drugs, Chinese Herbal; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Male; Myocardium; Pyrans; Rats; Rats, Sprague-Dawley

The effects of praeruptorin C (Pra-C) on cardiac dysfunction, myocardial compliance, and collagen content in renovascular hypertensive rats have been studied. In rats with left ventricular hypertrophy (LVH), the ratio of cardiac flow (CF)/heart wet weight (HWW) and cardiac output (CO)/HWW decreased by 20.1% and 35.5%; LVSP and -dp/dtmax decreased by 19.4% and 42.1%, while LVEDP and T value were increased by 186.4% and 226%. The left ventricular diastolic pressure-volume (P-V) curve was shifted to the left and down ward compared with that of sham-operated rats. The hydroxyproline content was 5.93 +/- 0.82 mg.g-1 dry weight in the left ventricular myocardial tissue of rats with LVH which was higher than that of sham-operated rats(e.g. 4.01 +/- 0.47 mg.g-1). The content did not change in the right ventricular myocardium. After treated with Pra-C for nine weeks, the CF/HWW and CO/HWW increased by 31.3% and 25.1%, the LVSP and -dp/dtmax increased by 16.7% and 27.8%. The LVEDP and T value was reduced by 34.9% and 36.5%, respectively, compared with those of LVH. The P-V curves of these rats were shifted to the right and in the up-ward direction. The hydroxyproline content was 4.52 +/- 0.3 mg.g-1 dry weight in the left ventricular tissue. These results indicate that Pra-C improved the cardiac contractility and relaxation by increasing the coronary flow and cardiac output, and decreasing the collagen content in the ventricular myocardium.

Topics: Animals; Calcium Channel Blockers; Collagen; Coumarins; Heart Function Tests; Hydroxyproline; Hypertension, Renovascular; Hypertrophy, Left Ventricular; In Vitro Techniques; Myocardial Contraction; Myocardium; Random Allocation; Rats; Rats, Sprague-Dawley