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+/-24 and 119+/-4 mmHg, respectively, n=16 each). DOCA-salt rats also showed a higher blood pressure (180+/-15 mmHg, n=18) compared with control (121+/-6 mmHg, n=14). VSM cells were enzymatically and mechanically isolated from basilar arteries. Single relaxed VSM cells measured 5 ~ 10 mum in width and 70 ~ 150 mum 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) calciumcurrents 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.
Animals ; Basilar Artery ; Blood Pressure ; Calcium Channels ; Calcium* ; Desoxycorticosterone ; Desoxycorticosterone Acetate ; Hypertension ; Hypertension, Renal* ; Microscopy ; Muscle, Smooth, Vascular* ; Rats ; Rats, Sprague-Dawley ; Renal Artery

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.
Aorta, Thoracic ; Blood Pressure ; Desoxycorticosterone* ; Guanylate Cyclase* ; Hypertension* ; Nitric Oxide ; Nitric Oxide Synthase ; Rats, Sprague-Dawley

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.
Animals ; Blotting, Western ; Desoxycorticosterone ; Hypertension ; Kidney ; Nitric Oxide* ; Nitrites ; Protein Isoforms ; Rats*

BACKGROUND: Effects of oxidative stress on the development of deoxycorticosterone acetate (DOCA)-salt or N(G)-nitro-L-arginine (L-NAME) hypertension were examined. METHODS: Male Sprague-awley rats were treated with DOCA (200 mg/kg, subcutaneous)-salt or L-NAME (40 mg/L in daily drinking water) for 4 weeks. To reduce the oxidative stress, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 3 mM/L) was cotreated in drinking water. The expression of endothelial nitric oxide synthase (eNOS) and nitrotyrosine proteins was determined in the renal cortex and thoracic aorta. RESULTS: Tempol prevented the development of DOCA-salt hypertension, whereas it was without effect on L-NAME hypertension. In DOCA-salt hypertension, the eNOS expression in the renal cortex was increased, the degree of which was attenuated by Tempol. The renal expression of nitrotyrosine was decreased, which was further decreased by Tempol. In the aorta, the expression of both eNOS and nitrotyrosine was decreased, which was not further affected by Tempol. In L-NAME hypertension, the renal expression of eNOS was significantly increased, which was blocked by Tempol. The expression of eNOS in the aorta was slightly decreased, and was not further affected by Tempol. The renal expression of nitrotyrosine was not significantly altered. However, its expression was significantly decreased in the aorta, and was further reduced by Tempol. CONCLUSION: The blockade of oxidative stress may attenuate the development of hypertension and provide tissue protection in DOCA-salt hypertension. The blockade of oxidative stress may also contribute to a tissue protection in L-NAME hypertension.
Animals ; Aorta ; Aorta, Thoracic ; Blood Pressure* ; Desoxycorticosterone ; Desoxycorticosterone Acetate ; Drinking ; Drinking Water ; Humans ; Hypertension* ; Male ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Nitric Oxide Synthase Type III ; Oxidative Stress* ; Rats

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 4-6 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.
Animals ; Arteries ; Baths ; Carotid Arteries ; Desoxycorticosterone Acetate ; Desoxycorticosterone* ; Drinking Water ; Genistein ; Humans ; Hypertension ; Male ; Muscle, Smooth, Vascular ; Phosphotransferases* ; Protein-Tyrosine Kinases ; Rats* ; Rats, Sprague-Dawley ; Relaxation ; Serotonin ; Signal Transduction ; Tyrosine*

17 -Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia that is characterized by primary amenorrhea, absence of secondary sex characteristics, hypertension, and a hypokalemic alkalosis that has resulted resulting from increased production of deoxycorticosterone and corticosterone by the adrenal. The diagnosis of this enzyme deficiency can be recognized by the increasing serum concentrations of steroid precursors, DOC and corticosterone and the decreasing concentrations of cortisol, and adrenal androgens. We diagnosed this in a 19 year old female who presented with primary amenorrhea. We report this case with a review of the literatures.
Adrenal Hyperplasia, Congenital ; Alkalosis ; Amenorrhea* ; Androgens ; Corticosterone ; Desoxycorticosterone ; Diagnosis ; Female ; Humans ; Hydrocortisone ; Hypertension ; Sex Characteristics ; Young Adult

PURPOSE: Baroreceptor reflex regulation has been shown to reset towards a higher blood pressure level. This study was designed to assess alterations of chronotropic baroreflexes in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Arterial pressure and heart rate (HR) were monitored continuously during intravenous infusions of phenylephrine or sodium nitroprusside. Ensuing reflex HR responses during each drug infusion were determined in two ways: (a) at 10 s intervals (time analysis), and (b) with every 10 mmHg change in pressure (pressure analysis). RESULTS: Both pressor and depressor responses produced by phenylephrine or sodium nitroprusside were comparable between normotensive and hypertensive rats. Both reflex tachycardia and bradycardia were attenuated in 2K1C hypertensive rats as compared with normotensive rats, whereas no significant differences were shown in DOCA-salt hypertensive rats. CONCLUSION: These results indicate that chronotropic baroreflexes are impaired in 2K1C hypertensive rats, but not in DOCA-salt hypertensive rats.
Animals ; Arterial Pressure ; Baroreflex ; Blood Pressure ; Bradycardia ; Desoxycorticosterone ; Dihydrotachysterol ; Heart Rate ; Hypertension ; Infusions, Intravenous ; Nitroprusside ; Phenylephrine ; Rats ; Reflex ; Tachycardia

As a process to study the mechanism of steroid hormones at the molecular level,the activities of lactic dehydrogenase (L.D.) and malic dehydrogenase (M.D.),NAD-linked transhydrogenases, were measured in the testis and the prostate. Ahundred male rabbits were divided into ten group as follows: Group 1: Control Group 2: Estrogen (6,000 units) injected Group 3: Androgen (1,200 unite)injected Group 4: Progesterone (1,200 units) injected Group 5: Hydrocortisone(30 mg) injected Group 6: DOCA (6 mg) injected Group 7: Castration control Group8: Castration and estrogen (6, OOO units) injected Group 9: Castration and androgen (1,200 units) injected Group 10: Castration and progesterone (1,200units) injected Changes in the activities of lactic dehydrogenase and malic dehydrogenase in theorganic tissues by exogenous steroid hormones were carefullyobserved. The lactic dehydrogenase activities were measured by the method of Wroblewski and La Due, and malic dehydrogenase activities by the Bodansky's modification of Porter's method. The results are as follows: 1) The control valueof L.D. activities in the testicular tissue of normal rabbits proved to be 89,400units per ram. The L.D. activities showed an increase up to 110.4 per cent in theestrogen injected group, 179.3 per cent in the androgen injected group and 147.0 per cent in the progesterone injected group, while the administration of hydrocortisone and DOCA decreased the value down to 85.2 per cent and 81.5 per cent, respectively. 2) The control value of M.D. activities in the testicular tissue of the normal rabbits was 23,600 units per gram. The M.D. activities showed an increase upto 111.4 per cent in the estrogen injected group. 191.1 per cent in the androgen injected group, and 156.8 per cent in the progesterone injected group, while the administration of hydrocortisone and DOCA decreased the value down to 85.2 per cent and 81.5 per cent, respectively. 3) In the prostate tissues of non-castrated rabbits, the L.D. activities were estimated normally to be 48,100 units per gram. The administration of sex hormone resulted in raising the activities upto 101.8 per cent in the estrogen injected group, 196.9 per cent in the androgen injected group and 153.9 per cent in the progesterone injected group. But the administration of hydrocortisone and DOCA decreased the value down to 92.5 per cent and 97.1 per cent, respectively. 4) In the prostate tissue of non-castrated rabbits, the control value of M.D. activities proved to be 14,600 unite per gram. The M.D. activities showed an increase upto 117.8 per cent in the estrogen injected group, 206.8 per cent in the androgen injected group and, 176.7 per cent in the progesterone injected group, while the administration of hydrocortisone and DOCA decreased the value down to 81.9 per cent and 95.2 per cent, respectively. 5) The prostatic L.D. activities were decreased to half the normal two weeks after castration. The administration of sex hormones (i.e., estrogen, androgen and progesterone) acted inclusively upon elevating the level f activities. Androgen, in general, was the most effective to restore the activity to the level of pre-castrated state. 6) The prostatic M.D. activities were also decreased to half the normal two weeks after castration. The administration of sex hormones acted inclusively upon elevating the level ofthe activities. Androgen had a remarkable effect in elevating the M.D. activities, which showed twice the precastration level. In this study, it is concluded that L.D. and M.D. activities are present in the testis and the prostate. They are induced and activated by the administration of sex hormones, of which androgen has the most remarkable effect, and estrogen and progesteronehave less effect, while hydrocortisone and DOCA are ineffective in some cases orinhibitory in others.
Castration* ; Desoxycorticosterone Acetate ; Estrogens ; Gonadal Steroid Hormones ; Humans ; Hydrocortisone ; Malate Dehydrogenase* ; Male* ; Oxidoreductases ; Progesterone ; Prostate* ; Rabbits* ; Testis*

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.
Animals ; Aorta, Thoracic ; Arterial Pressure ; Blotting, Western ; Desoxycorticosterone ; Hypertension* ; Isoenzymes ; Nitric Oxide Synthase* ; Nitric Oxide* ; Nitrites ; Protein Isoforms ; Rats ; Vasodilation

The pathophysiological implications of aldosterone and adrenomedullin in the cardiac ventricular hypertrophy were examined. Male Sprague-Dawley rats were treated with deoxycorticosterone acetate (DOCA)-salt and monocrotaline (MCT) to selectively elicit left and right ventricular (LV, RV) hypertrophy, respectively. The mRNA expression of aldosterone synthase and adrenomedullin in LV and RV was determined by reverse transcription-polymerase chain reaction. The expression of aldosterone synthase and adrenomedullin was increased in LV, while not altered significantly in RV of DOCA-salt-treated rats. On the contrary, the expression was not significantly altered in LV, but increased in RV of MCT-treated rats. The enhanced expression of aldosterone synthase may be causally related with the development of ventricular hypertrophy, and the increased expression of adrenomedullin may act as a counter-regulatory mechanism.
Adrenomedullin* ; Aldosterone Synthase* ; Aldosterone* ; Animals ; Desoxycorticosterone ; Humans ; Hypertrophy ; Hypertrophy, Right Ventricular* ; Male ; Monocrotaline ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger