• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.3
• /
• pp.315-320
• /
• 1999

Molecular regulation of the renin-angiotensin system (RAS) was investigated in deoxycorticosterone acetate (DOCA)-salt hypertension. The expression of renin, angiotensinogen and angiotensin II receptor genes in the kidney and liver was determined by Northern blot analysis in rats which were made DOCA-salt hypertensive over the period of 2 or 4 weeks. Along with the hypertension, renin mRNA was decreased in the remnant kidney. The expression of angiotensinogen gene was not significantly altered in the kidney, but was significantly decreased in the liver. The expression of angiotensin II receptor gene was increased in the kidney, while it remained unaltered in the liver. The duration of hypertension did not affect the altered gene expression. It is suggested that the components of RAS are transcriptionally regulated in DOCA-salt hypertension in a tissue-specific manner.

• The Korean Journal of Physiology and Pharmacology
• /
• v.4 no.5
• /
• pp.379-383
• /
• 2000

Pathophysiological implications of the vascular nitric oxide (NO)/cGMP pathway in hypertension were investigated. Sprague-Dawley rats were made deoxycorticosterone acetate (DOCA)-salt hypertensive for six weeks. The protein expression of endothelial constitutive NO synthase (ecNOS) and the tissue content of NO were determined in the thoracic aorta. The protein expression and catalytic activity of soluble guanylyl cyclase (GC) were also determined. Systolic blood pressure measured on the day of experiment was significantly higher in the experimental group than in the control. The hypertension was associated with decreases in the vascular tissue content of NO metabolites, concomitantly with the expression of ecNOS proteins. The protein expression of GC was not affected, while its catalytic activity was significantly decreased in hypertension. These results indicate that the high blood pressure is associated with a decreased activity of vascular NO/cGMP pathway in DOCA-salt hypertension.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.4
• /
• pp.455-460
• /
• 1998

The present study was aimed at investigating whether the development of hypertension is related with an altered expression of nitric oxide synthases (NOS) in the kidney. By Western blot analysis, the expression of bNOS and ecNOS isoforms was determined in the kidney of deoxycorticosterone acetate (DOCA)-salt and two-kidney, one clip (2K1C) rats. In DOCA-salt hypertension, the expression of both bNOS and ecNOS was decreased, along with tissue contents of nitrites. In 2K1C hypertension, the nitrite content of the clipped kidney was decreased along with ecNOS levels, whereas neither the nitrite content nor the expression of NOS isoforms was significantly altered in the contralateral non-clipped kidney. These results suggest that the development of hypertension is associated with an altered renal expression of NOS and nitric oxide generation in DOCA-salt and 2K1C rats.

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.3
• /
• pp.253-258
• /
• 2001

The present study was aimed to examine whether the expression of renin is associated with that of cyclooxygenase-2 (COX-2) in the kidney. Male Sprague-Dawley rats were made two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertensive, to stimulate or to inhibit the endogenous renin-angiotensin system, respectively. The expression of renin and COX-2 mRNA was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. 2K1C hypertensive rats showed an increased expression of renin as well as of COX-2 in the clipped kidney. The expression of renin was decreased in parallel with that of COX-2 in the contralateral non-clipped kidney. Removal of the renal arterial clip reversed the expression of both genes, along with the blood pressure, to the control level. On the other hand, DOCA-salt hypertension was associated with parallel decreases of renin and COX-2 expression. These results indicate that renin and COX-2 genes are coordinately expressed in the kidney.

• Advances in Traditional Medicine
• /
• v.8 no.4
• /
• pp.354-364
• /
• 2008

The present study was carried out to investigate the antihypertensive effect of a folklore herbal formulation (HF) (300mg/kg/day; p.o.) in deoxycorticosterone acetate (DOCA)-salt induced and fructose induced hypertensive rats. In DOCA model, DOCA (15 mg/kg, s.c., twice a week) was administered to unilateral nephrectomized rats for 4 weeks. In fructose model, drinking water was replaced with 10% fructose solution for 6 weeks to induce hypertension. Systolic blood pressure (BP) was measured once every week during the treatment schedule. After completion of treatment schedule, BP and vascular reactivity to various agonists like Noradrenaline, Adrenaline, Phenylephrine and Serotonin (5-hydroxytrptamine; 5-HT) were recorded in rats of both models. A cumulative concentration response curve of 5-HT was carried out in isolated rat fundus strip of the DOCA-salt induced and fructose induced hypertensive rats. The results tend to suggest that HF possesses antihypertensive activity.

• The Korean Journal of Physiology and Pharmacology
• /
• v.8 no.3
• /
• pp.147-151
• /
• 2004

The present study was undertaken to determine the regulation of heat shock proteins (HSP) in the kidney in hypertension. Two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertension was induced in male Sprague-Dawley rats. At weeks 1 and 4 after inducing the hypertension, the expression of HSP70, HSP32 and HSP25 was determined in the kidney by Western blot analysis. In 2K1C hypertension, the expression of HSP70, HSP32 and HSP25 was increased in the clipped kidney at both weeks 1 and 4. However, in the contralateral kidney, their expression was not significantly altered at week 1, but increased at week 4. In DOCA-salt hypertension, the expression of HSP remained unaltered in the remnant kidney at week 1, but significantly increased at week 4. These results indicate that HSP are differentially regulated in the kidney according to the duration and the model of hypertension.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.5
• /
• pp.547-553
• /
• 1997

It has been known that activation of tyrosine kinases is involved in signal transduction. Role of the tyrosine kinase in vascular smooth muscle contraction was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Male Sprague-Dawley rats underwent uninephrectomy, one week after which they were subcutaneously implanted with DOCA (200 mg/kg) and supplied with 1% NaCl and 0.2% KCl drinking water for $4{\sim}6$ weeks. Control rats were treated the same except for that no DOCA was implanted. Helical strips of carotid arteries were mounted in organ baths for measurement of isometric force development. Genistein was used as a tyrosine kinase inhibitor. Concentration-response curves to 5-hydroxytryptamine (5-HT) shifted to the right by genistein in both DOCA-salt hypertensive and control rats. Although the sensitivity to genistein was similar between the two groups, the maximum force generation by 5-HT was less inhibited by genistein in arteries from DOCA-salt hypertensive rats than in those from controls. Genistein-induced relaxations were attenuated in arteries from DOCA-salt rats. Genistein affected the contraction to phorbol 12, 13-dibutyrate (PDBu) neither in DOCA-salt nor in control arteries. These observations suggest that tyrosine kinase is involved in 5-HT-induced vascular contraction, of which role is reduced in DOCA-salt hypertension.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.3
• /
• pp.351-356
• /
• 1999

The present study was aimed at investigating whether the calcium current in the vascular smooth muscle (VSM) cells is altered in renal hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in Sprague-Dawley rats. Rats without clipping the renal artery or implanting DOCA were used as control for 2K1C and DOCA-salt hypertension, respectively. Four weeks after clipping, systolic blood pressure was significantly higher in 2K1C rats than in control $(192{\pm}24\;and\;119{\pm}4$ mmHg, respectively, n=16 each). DOCA-salt rats also showed a higher blood pressure $(180{\pm}15$ mmHg, n=18) compared with control $(121{\pm}6$ mmHg, n=14). VSM cells were enzymatically and mechanically isolated from basilar arteries. Single relaxed VSM cells measured $5{\sim}10\;{\mu}m$ in width and $70{\sim}150\;{\mu}m$ in length were obtained. VSM cells could not be differentiated in size and shape between hypertensive and normotensive rats under light microscopy. High-threshold (L-type) calcium currents were recorded using whole-cell patch clamp technique. The amplitude of the current recorded from VSM cells was larger in 2K1C hypertension than in control. Neither the voltage-dependence of the calcium current nor the cell capacitance was significantly affected by 2K1C hypertension. By contrast, the amplitude of the calcium current was not altered in DOCA-salt hypertension. These results suggest that high-threshold calcium current of the VSM cells is altered in 2K1C hypertension, and that calcium channel may not be involved in calcium recruitment of VSM in DOCA-salt hypertension.

• The Korean Journal of Physiology and Pharmacology
• /
• v.4 no.1
• /
• pp.55-61
• /
• 2000

The present study was conducted to investigate the possible role of the sympathetic nervous system in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension. 2K1C and DOCA- salt hypertension were made in Sprague-Dawley rats. Four weeks after induction of hypertension, systolic blood pressure measured in conscious state was significantly higher in 2K1C $(216{\pm}18\;mmHg)$ and DOCA-salt $(205{\pm}29\;mmHg)$ groups than that in control $(128{\pm}4\;mmHg).$ The third branches (＜300 ${\mu}m$ in outer diameter) of the mesenteric artery were isolated and cut into ring segments of $2{\sim}3$ mm in length. Each ring segment was mounted in tissue bath and connected to a force displacement transducer for measurement of isometric tension. The arterial rings were contracted by application of norepinephrine (NE) in a dose-dependent manner. The amplitude of the NE-induced contraction of the vessels was significantly larger in hypertension than in control. The NE-induced contraction was significantly enhanced by neuropeptide Y (NPY) in hypertension. Reciprocally, NPY-elicited vasocontraction was increased by NE in hypertension. These results suggest that the sympathetic nervous system contributes to the development of 2K1C and DOCA-salt hypertension.

• Journal of Chest Surgery
• /
• v.32 no.2
• /
• pp.138-143
• /
• 1999

Background: The endothelium-dependent vasorelaxation has been largely accounted for by the release of nitric oxide (NO). Three distinct isoforms of NO synthases (NOS) have been characterized, i.e., brain(bNOS), inducible (iNOS), and endothelial constitutive (ecNOS). Although hypertension hasbeen associated with a vascular endothelial dysfunction, changes in the vascular expression of NOS isoforms have not been established. The present study was aimed at exploring the vascular expression of NOS isozymes in hypertension. Material and Method: Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were induced in rats. The expression of different NOS isozymes in the thoracic aorta was determined by Western blot analysis. The vascular tissue contents of nitrites were measured by colorimetric assay. Result: Arterial blood pressure was significantly higher in experimental groups of 2K1C and DOCA-salt rats compared with their corresponding control rats. The vascular expression of bNOS as well as that of ecNOS was decreased in both models of hypertension. iNOS was not changed in DOCA-salt hypertension, but was also decreased in 2K1C hypertension. The vascular contents of nitrites were significantly decreased in DOCA-salt as well as in 2K1C hypertension. Conclusion: These results suggest that 2K1C and DOCA-salt hypertension are associated with decreases in the vascular expression of NOS isozymes and nitrite contents.