• 대한한의학방제학회지
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• 제28권3호
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• pp.271-280
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• 2020

Hypertension has been approved to cause disharmony between the heart and kidney such as cardiac hypertrophy and kidney dysfunction. In traditional oriental medicine Paeo-tang (PET) has been shown to have effects on blood circulation improvement. However, the beneficial effect of PET on hypertension remains unknown. In this study, we investigated that PET attenuates blood pressure and improves cardiovascular and renal function in NG-nitro-L-arginine methylester (L-NAME) rat model. Hypertensive rat models were induced by the administration of L-NAME (40 mg/kg/day) and then PET (50 or 100 mg/kg/day) or Olmetec was treated for 2 weeks. PET treatment significantly suppressed the systolic blood pressure and decreased intima-media thickness in the thoracic aorta. PET ameliorated endothelium-dependent and independent vascular relaxation in the L-NAME-induced vascular dysfunction. PET ameliorated the functional decline in the kidney such as albumin and blood urea nitrogen in plasma. These results demonstrated that PET possesses protective effects against L-NAME-induced hypertension.

• 약학회지
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• 제37권6호
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• pp.605-614
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• 1993

To investigate the endothelial dependence of angiotensin II(A II)-induced responses in the systemic and pulmonary arterial system of acute renal hypertensive rats of 2-kidney, 1-ligation type (RHRs), A II-induced vasocontractile and pressor effects were evaluated in isolated arteries and in vivo, respectively. A II dose-dependently contracted intact thoracic aorta and pulmonary artery (E$_{max}$:40% at 10$^{-7}$M and 80% at 3$\times$10 $^{-8}$M, respectively) from normotensive rats(NRs), which was significantly increased by removal of endothelial cells or pretreatment with EDRF inhibitors. In NRs, A II increased mean systemic and pulmonary arterial pressure(33 and 5.6mmHg at 0.1 $\mu\textrm{g}$/kg, respectively), the effect being significantly increased (P<0.01) by L-NAME(30mg/kg, i.v.). However, A II-induced contraction of intact thoracic aorta and pulmonary artery(E$_{max}$: 33% at 10$^{-7}$M and 93% at 3$\times$10$^{-8}$M, respectively) from RHRs were not changed after endothelial function was disrupted as above; similarly, pressor effects of A II on the systemic and pulmonary arterial pressure in RHRs did not altered by L-NAME. A II tachyphylactic responses for intact thoracic aorta from NRs and RHRs(65 and 87% at 10$^{-8}$M, respectively) were greater than those for pulmonary artery(19 and 19% at 10$^{-8}$M, respectively). Distruption of endothelial function significantly (P<0.01) depressed A II tachyphylaxis for thoracic aorta, but not for pulmonary artery. These results suggest that vascular reactivity to A II is not altered in RHRs, and it is greater for pulmonary arterial system than for systemic arterial system. A II reactivity is EDRF-dependent in both arterial systems of NRs, but EDRF-independent for RHRs. Finally, EDRF is one of the major factors underlying A II tachyphylaxis for thoracic aorta, but not for pulmonary artery.

• 동의생리병리학회지
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• 제18권1호
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• pp.84-92
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• 2004

The present study examined the effects of Taekunyukmijiwhang-tang (TV) on blood pressure and renal function in nitric oxide (NO)-dependent hypertensive rats. A phamacological inhibition of nitric oxide synthase (NOS) for 4-6 weeks produces renal vasoconstriction, renal dysfunction, and progressive severe hypertension. Treatment of rats with NG-Nitro-L-arginie methylester (L-NAME) (100 mg/L, 6 weeks), which is a nonspecific NOS inhibitor, cause a sustained increase in systolic blood pressure (SBP), along with the decrease in expression of ecNOS in the kidney and thoracic aorta. The expression of Na, K-ATPase α1 subunit in the kidney was also reduced in the L-NAME induced hypertensive rats group. The renal functional parameters including urine osmolality (Uosm), creatinine clearance (Ccr), which is an index of glomerular filtration (GFR) were decreased in rat with L-NAME induced hypertension. while solute-free water reabsoption (TcH₂O) was unchanged in all experimental group. However, the group combined treated with TV and L-NAME did not develop hypertension and expression of ecNOS in the aorta was restored. The expression of Na/sup +/, K/sup +/-ATpase α1 subunit in the kidney was markedly restored in L-NAME-induced hypertension rats by administration of TV along with the restoration of urinary volume (UV) and sodium excretion (UNaV), whlie Na/sup +/, K/sup +/-ATPase /β1 subunit was not altered. These results suggest that TV attenuates an increase in SSP in the L-NAME induced hypertension and restores partially renal function, which seems to be caused by up-regulation of expression of Na/sup +/, K/sup +/-ATPase α1 subunit in the kidney and ecNOS in thoracic aorta.

• Korean Journal of Acupuncture
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• 제25권2호
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• pp.199-210
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• 2008

Objectives : This study was performed to investigate the effect of invasive laser acupuncture therapy with green light (LAT-G) at HT7(Sinmun), SP3(Taebaek) on the blood pressure in hypertensive rat induced by two kidney one clip. Methods : The experiments were performed on Sprague Dawley rats. 2K1C hypertension model was prepared by constricting the left renal artery with a sliver clip. Animals were divided into four groups, which were simple acupuncture treatment group with straight needle insertion on the square(AT-SS), acupuncture treatment group with reducing manipulation in the opposite channel direction(AT-RD), laser acupuncture treatment group with green light 532 nm, 10mW power in the opposite channel direction(LAT-G10) and laser acupuncture treatment group with green light 532 nm, 20mW power in the opposite channel direction(LAT-G20). The treatments were performed once per two days for 10 days. Results : Body weight was increased significantly in LAT-G20 group compared with AT-RD group. The blood pressure was significantly decreased in LAT-G20 and LAT-G10 groups compared with AT-SS group. Conclusions : These results suggest that green laser acupuncture therapy at SP3 ${\cdot}$ HT7 is more effective than straight needle insertion on the square for controlling hypertension. It is possible that invasive green laser acupuncture therapy (532 nm) can be used as a reducing method of the traditional acupuncture techniques.

• The Korean Journal of Physiology
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• 제30권2호
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• pp.269-278
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• 1996

The mechanism of impaired endothelium-dependent relaxation in the aorta of one-kidney, one clip Goldblatt hypertensive (1K,1C-GBH) rats was investigated. 8 week-old Wistar-Kyoto (WKY) rats were made hypertensive by left renal artery stenosis with contralateral nephrectomy. Endothelium-dependent relaxation was significantly reduced in 1K,1C-GBH rats as compared with WKY rats. However, the relaxation by sodium nitroprusside in 1K,1C-GBH rats was not reduced as compared with WKY rats. The impairment of endothelium-dependent relaxation in 1K,1C-GBH rats was partially restored by the pretreatment of indomethacin or SQ29548. When the nitric oxide production was inhibited by L-nitroarginine methyl ester, acetylcholine (ACh) induced a endothelium-dependent contraction that was greater in 1K,1C-GBH rats than in WKY rats. Endothelium-dependent contraction by ACh was completely abolished by indomethacin or SQ29548. However, imidazole, tranylcypromine and superoxide dismutase did not affect the endothelium-dependent contraction in 1K,1C-GBH rats. These results suggest that impaired endothelium-dependent relaxation in the 1K,1C-GBH rats might be due to the simultaneous release of EDCF, and that prostaglandin B2 may be involved as a mediator of endothelium-dependent contraction.

• Archives of Pharmacal Research
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• 제14권3호
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• pp.242-248
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• 1991

Antihypertensive effect of YH 334 was examined in various experimental hypertension rat models and the systemic and regional hymohynamic profiles of the compound were investigated in conscious spontaneously hypertensive rats (SHR). The antiypertensive potensive potency of YH 334 is found to be more than 10 times stronger than that of nitrendipine in the all hypertensive models. The effective doses to lower the initial blood pressure by 20% $(ED_{20})$ of YH334 were 1.4 mg/kg in normotensive rats (NR), 0.7 mglkg in SHR. 0.1 mg/kg in DOCA salt hypertensive rats (DHR) and 0.4 mg/kg in renal hypertensive rats (RHR), and the $ED_{20}$ values of nitrendipine were 15.8 mg/kg in NR, 7.1 mg/kg in SHR, 1.7 mg/kg in DHR and 4.8 mg/kg in RHR. The primary hemodynamic effect hemodynamic profile is similar to that of nitrendipine. Both compounds seem to produce potent antihypertensive effects by lowering peripheral resistance in the skeletal muscles. In the organ bath study using isolated rabbit aorta, YH 334 was found to be a potent voltage dependent calcium channel blocker without significant inhibitory effect on the receptor operated calcium channels like the most of other dihydropyridine type calcium antagonists. Furthermore, YH334 showed acute diuretic and natriuretic effects in conscious SHR, which may render the unnecessary restriction of sodium in the diet of those patients on long term hypertension therapy. This effect would provide an additional benefit to its potent antihypertensive activity.

• Archives of Pharmacal Research
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• 제17권4호
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• pp.263-268
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• 1994

This study was conducted to characterize the in vivo pharmacology of KR-30988, KR-30992 and losartan, new AT antagonists, given as i.v. cumulative doses, in two antimal models of high renin, conscious renal artery-ligated hypertensinve rats (RHRs) and nomotensive rats anesthetized with urethane (90 mg/kg, i.p.) and .alpha.-chloralose (90 mg/kg, i.p.), with a special emphasis on the phamacological characterization of the latter model. In conscious RHRs, KR-30988, KR-30992, losartan and captopril caused a dose-dependent decrease in blood pressure, their relative potencise ($ED_{20}$) being 0.057, 0.028, 0164 and 0.018 mg/kg, i.v., repectively. In anesthetized rats, 2 hours after anesthesia, plasma renin activity was increased from 7.31 tp 34.07 ng/ml/h, the level approximately 1.5 times greater than the highest level in RHRs. In anesthtized rats, the $ED_{20}$s for all four compounds were 0.004 mg/kg i.v., respectively. By comparison, $ED_{20}$sfrom anesthetized rats were 4 to 5 times smaller than those from conscious RHRs, with a good correlation (.gamma. = 0.999) noted between thetized rats to the hypotensive activity of the compounds and the same order of potencies intwo models. These results suggest that, in addition to PHRs, the normotensive rats anesthetized as above can serve as a suitable model for the rapid phamacological evaluation of $AT_1$ receptor antagonists.

• The Korean Journal of Physiology
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• 제30권1호
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• pp.21-31
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• 1996

To investigate the mechanisms of increased endothelium-dependent contraction by acetylcholine in hypertensive rats, the relationship between endothelium-dependent contraction by acetylcholine and blood pressure was studied in spontaneously hypertensive rats (SHR), one-kidney, one clip Goldblatt hypertension (1K,1C-GBH) rats, and Wistar-Kyoto rats (WKY). SHR were treated orally with enalapril or nicardipine in order to prevent development of hypertension or suppress the developed hypertension. 1K,1C-GBH rats were made by renal artery stenosis with contralateral nephrectomy in 8 week-WKY. 1. Endothelium-dependent contractions by acetylcholine $(10^{-6}{\sim}10^{-5}\;M)$ in SHR were significantly greater than those in WKY. 2. Chronic treatment with enalapril or nicardipine reduced the endothelium-dependent contraction in SHR 3. The degree of reduction of endothelium-dependent contraction was greater in SHR which was prevented from developing hypertension than in SHR of which high blood pressure was suppressed. 4. In aortic rings from 1K,1C-GBH rats, endothelium-dependent contractions by acetylcholine were augmented as compared with WKY. 5. There is good relationship between the value of blood pressure and magnitude of endothelium-dependent contraction. Thus, it is suggested that increased endothelium-dependent contraction in hypertensive rats may he due to the high blood pressure and endothelium-dependent contraction may not be a cause of the initiation of hypertension in SHR.

• The Korean Journal of Physiology
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• 제20권2호
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• pp.236-248
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• 1986

Alterations of renin-angiotensin system have been suggested as one of the mechanisms increasing arterial blood pressure in experimental and clinical hypertension. But the exact nature of high blood pressure in the early and late phase of renal hypertension is still controversial. To clarify the nature of renin release in both unclipped and clipped kidney of two kidney one clip Goldblatt lypertensive rat, experiments have been done in kidney slices, which were obtained from the rats of 3 and 7 days of operation. Basal rate of renin release was suppressed in unclipped kidney slices compared to clipped kidney Norepinephrine increased renin release from unclipped kidney slices, but not from clipped kidney slices. Suppressions by angiotensin Il and arginine vasopressin of renin release were attenuated in the clipped kidney slices compared to unclipped and sham-operated kidney slices. Increases by verapamil and trifluoperazine of renin release were attenuated in the clipped kidney slices compared to unclipped and sham-operated kidney slices. These results suggest that the negative feedback control mechanism of the renin-angiotensin system by angiotensin Il and arginine vasopressin is attenuated in the clipped kidney of two kidney one clip Goldblatt hypertensive rat, and that one of the altered mechanisms may be caused by certain regulatory changes of intracellular calcium and/or calcium-calmodulin complex in the juxtaglomerular cells.

• Korean Journal of Acupuncture
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• 제19권1호
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• pp.47-56
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• 2002

The frequency of the hypertension is increasing as the life level is improved and an average span of the life is extended since we approached modern stage. The hypertension is also dangerous disease which raises fatal complication for example with the bleeding aproplexy and the ischemic attack. The medicinal treatment about the hypertension is required patients to take continually. The acupuncture have been introduced because a medicine-chemical treatment hasn't good influence on the human body. It recently has been processed that studies acupuncture effect for blood pressure and have been found out that blood pressure go down. The object of this study observe the effect of LR3 acupuncture on hypertension in Renal Hypertension RAT induced by 2K1C. The 2K1C model was based on renin-angiotensin system. We put the silver clip in renal artery to induce renal hypertension. We try to observe that LR3 acupuncture influence on the blood pressure and c-fos expression in CVLM, NTS, RVLM. In results, the blood pressure was decreased during acupuncture than before acupuncture, after acupuncture. The heart rate was also decreased during acupuncture than before acupuncture, after acupuncture. The LR3 acupuncture significantly effects on blood pressure and heart rate (P<0.05). The increased expression of c-fos was shown in CVLM, NTS, but not in RVLM. In conclusion, LR3 was relived the action of control upon the hypertension and related with medulla, particularly CVLM, NTS. It needs to be closely examined pharmacological mechanism and studied combination with other acupoints.