Cortistatin attenuates vascular calcification in rats

Cortistatin (CST) is a newly discovered polypeptide with multiple biological activities that plays a regulatory role in the nervous, endocrine and immune systems. However, the role of CST in the pathogenesis of cardiovascular diseases remains unclear. In this study, we investigated in rats whether CST inhibits vascular calcification induced by vitamin D3 and nicotine treatment in vivo and calcification of cultured rat vascular smooth muscular cells (VSMCs) induced by beta-glycerophosphate in vitro and the underlying mechanism. We measured rat hemodynamic variables, alkaline phosphatase (ALP) activity, calcium deposition and pathological changes in aortic tissues and cultured VSMCs. CST treatment significantly improved hemodynamic values and arterial compliance in rats with vascular calcification, by decreasing systolic blood pressure, pulse pressure, left ventricular end-systolic pressure and left ventricular end-diastolic pressure. CST also significantly decreased ALP activity and calcium deposition, alleviated pathological injury and down-regulated the mRNA expression of type III sodium-dependent phosphate co-transporter-1 (Pit-1) in aortic tissues. It dose-independently inhibited the calcification of VSMCs by decreasing ALP activity and calcium deposition, alleviating pathologic injury and down-regulating Pit-1 mRNA expression. As with CST treatment, ALP activation and calcium deposition were decreased significantly on treatment with ghrelin, the endogenous agonist of growth hormone secretagogue receptor 1a (GHSR1a), but not significantly with somatostatin-14 or proadrenomedullin N-terminal 20 peptide in VSMCs. Further, growth hormone-releasing peptide-6[D-lys], the endogenous antagonist of GHSR1a, markedly reversed the increased ALP activity and calcium deposition in VSMCs. CST could be a new target molecule for the prevention and therapy of vascular calcification, whose effects are mediated by GHSR1a rather than SSTRs or Mrg X2.     

1,25-dihydroxyvitamin D3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D

Several studies have demonstrated that excess of vitamin D3 is toxic particularly to vascular tissues. A notable pathological feature is arterial calcification. The nature of the toxic metabolite in hypervitaminosis D and the pathogenesis of arterial calcification are not clearly understood. The present study was undertaken to explore whether arterial calcification is a sequel of increased calcium uptake by arterial smooth muscle mediated by up regulation of vitamin D receptor in the cells in response to elevated circulating levels of vitamin D3 in serum. The experimental study was performed in 20 New Zealand white female rabbits aged 6 months. Animals in the test group were injected 10,000 IU of cholecalciferol intramuscularly twice a week for one month. Six control animals were given intra-muscular injections of plain cottonseed oil. Animals were sacrificed and aortas were examined for pathological lesions, 1,25-dihyroxyvitamin D3 (1,25(OH)2 D3) receptor levels and 45Ca uptake in smooth muscle cells. Serum samples collected at intervals were assayed for levels of 25-OH-D3 and calcium. The results showed that in animals given injections of cholecalciferol, serum levels of 25-OH-D3 were elevated. In four of these animals calcification and aneurysmal changes were seen in the aorta. Histological lesions comprised of fragmentation of elastic fibers as well as extensive loss of elastic layers. 1,25(OH)2 D3 receptor levels were up regulated and 45Ca uptake enhanced in aortas of animals which were given excessive vitamin D3. The evidences gathered suggest that excess vitamin D is arteriotoxic and that the vitamin induces arterial calcification through up regulation of 1,25(OH)2D3 receptor and increased calcium uptake in smooth muscle cells of the arteries.     

补镁对大鼠血管钙化的影响

目的:在大鼠血管钙化模型上,观察外源性补充硫酸镁对大鼠血管钙化的影响,以探讨硫酸镁在血管钙化中作用及机制。方法:用维生素D3加尼古丁诱导大鼠血管钙化,von Kossa染色、钙含量测定及碱性磷酸酶活性测定判断血管钙化程度;用半定量RT-PCR方法测定血管钙化标志分子骨桥蛋白mRNA水平;用生物化学方法测定血管一氧化氮(NO)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量。结果:钙化组大鼠血压升高,收缩压较对照组高27%(P<0.05);血管von Kossa染色见血管中膜弹性纤维间可见大量棕黑色颗粒沉积,主动脉钙含量及碱性磷酸酶活性分别较对照高3.9倍和3.4倍(P<0.01),钙化血管组织骨桥蛋白mRNA表达上调40%(P<0.01),血管钙化后可加重血管组织过氧化损伤;而诱导钙化后外源性补充硫酸镁可减轻血管钙化程度,与钙化组比较,低、高剂量硫酸镁组均明显缓解上述指标的变化。结论:诱导血管钙化后外源性补充硫酸镁可以减轻大鼠血管钙化和血管损伤程度。     

大鼠动脉钙化诱导过程中炎症小体复合物分子的变化

目的:以SD大鼠动脉钙化为模型,研究钙化发生过程中炎症小体复合物分子的变化。方法:大鼠皮下注射维生素D3诱导动脉钙化,并用HE染色检测动脉钙化的发生,用半定量PCR测定钙化发展过程中细胞内NALP3炎症小体复合物核心蛋白NALP3、ASC和Caspase-1的mRNA水平变化。结果:随着动脉钙化的发展,细胞内NALP3、ASC和Caspase-1的mRNA表达水平逐步增加。结论:构建了大鼠动脉钙化模型,并且发现NALP3炎症小体复合物在动物钙化诱导过程中表达增加,为进一步研究动脉钙化的机制及筛选抗动脉硬化药物打下基础。     

Impaired NO-dependent inhibition of store- and receptor-operated calcium entry in pulmonary vascular smooth muscle after chronic hypoxia

We have recently demonstrated that chronic hypoxia (CH) attenuates nitric oxide (NO)-mediated decreases in pulmonary vascular smooth muscle (VSM) intracellular free calcium concentration ([Ca2+]i) and promotes NO-dependent VSM Ca2+ desensitization. The objective of the current study was to identify potential mechanisms by which CH interferes with regulation of [Ca2+]i by NO. We hypothesized that CH impairs NO-mediated inhibition of store-operated (capacitative) Ca2+ entry (SOCE) or receptor-operated Ca2+ entry (ROCE) in pulmonary VSM. To test this hypothesis, we examined effects of the NO donor, spermine NONOate, on SOCE resulting from depletion of intracellular Ca2+ stores with cyclopiazonic acid, and on UTP-induced ROCE in isolated, endothelium-denuded, pressurized pulmonary arteries (213 +/- 8 microm inner diameter) from control and CH (4 wk at 0.5 atm) rats. Arteries were loaded with fura-2 AM to continuously monitor VSM [Ca2+]i. We found that the change in [Ca2+]i associated with SOCE and ROCE was significantly reduced in vessels from CH animals. Furthermore, spermine NONOate diminished SOCE and ROCE in vessels from control, but not CH animals. We conclude that NO-mediated inhibition of SOCE and ROCE is impaired after CH-induced pulmonary hypertension.     

Natural incidence of interruptions in the internal elastic lamina of caudal and renal arteries of the rat

Interruptions in the internal elastic lamina (IEL) have been quantified by light microscopy in the caudal arteries of different strains of rats and in caudal and renal arteries of (i) male and female virgin rats up until 2 years of age, (ii) repeatedly bred rats and (ii) hypertensive rats. Results showed that gaps in the IEL exist in caudal arteries of adult males in all strains studied, but to a lesser extent in the hairless mutant. In the virgin Wistar rat these interruptions in the IEL form with age in both caudal and renal arteries, and are more numerous (i) in the male than in the female in both arteries, and (ii) in the caudal than in the renal artery in both sexes. Repeated breeding in the Wistar rat abolishes the sex difference in incidence of IEL gaps in both renal and caudal arteries. The Sprague-Dawley breeder rat is more susceptible than the Wistar breeder to their formation in the renal artery. Hypertension in the male consistently increases the formation of IEL gaps in the renal but not in the caudal artery. The importance of local factors, e.g. hemodynamics, in the formation of these defects in the IEL, and their possible relationship with the development of arteriosclerosis is discussed.     

筛选大鼠血管钙化消退差异表达基因及初步分析

目的：探讨大鼠在血管钙化消退过程中基因表达的变化。方法：选取6周龄SPF级雄性SD大鼠24只,随机分成3组（n=8）,分别为对照组、钙化组和消退组。钙化组和消退组制作血管钙化模型（vitamin D3 plus nieotine,VDN）,对照组生理盐水和花生油灌胃。钙化组和对照组于实验第8周处死,消退组继续饲养至16周处死,测定各组大鼠动脉组织钙含量并作病理检查。采用抑制性消减杂交方法将消退组和钙化组大鼠血管cDNA作差减杂交,分离消退组较钙化组高表达或低表达基因的cDNA片段,建立消退组和钙化组的差异表达文库,扩增、鉴定文库并测序阳性克隆,BLAST比对测序序列。随机挑选4个基因进行RT-PCR验证和DNA条带半定量分析。结果：①血管组织钙含量测定显示钙化组（（15．34±2．51）mg／g）较对照组（（5．20±0．75）mg／g）血管组织钙含量明显升高（P〈0．01）;消退组（（12．73±1．89）mg／g）较钙化组降低（P〈0．05）;②构建了血管钙化的差减文库,对所获阳性克隆进行测序和BLAST比对分析,获得28个表达上调基因和22个表达下调基因。RT-PCR验证示Prdx3,Ank2,Ror2,Abcel等基因在消退组和钙化组间差异表达,消退组较钙化组表达增高,平均约为后者的1．7倍。结论：VDN模型诱导的大鼠血管钙化可以发生主动消退。钙化消退过程中焦磷酸合成相关基因、谷氨酸信号相关基因、还原及凋亡调节基因表达上调,同时见较多骨化相关基因及氧化活性等基因表达下调。钙化抑制基因的表达增多而钙化促进基因表达的下降可能是钙化发生主动消退的内源性机制。     

Optical measurement of age-related calcification in human blood vessels

Vascular calcification is commonly associated with aging. Quantification of calcium accumulation in vessel walls is important in understanding the mechanisms of vascular calcification. To elucidate age-related change of calcification, site dependence of calcification, and the effect of hemodynamic stress on calcification, we measured calcium contents in various blood vessels with atomic emission spectrometry and simulated blood flow in the vessels by computational fluid dynamics. The content of calcium in the arteries increased progressively with aging while there is no change in the veins. The higher accumulation of calcium occurred in the arteries of the lower limb in comparison to the arteries of the upper limb. In the arterial bifurcation, there was the correlation at hemodynamic stress distribution and calcium content. The results of this study quantitatively support clinical findings of nonuniform calcification, and suggest that hemodynamic stress affects vascular calcification.     

Myogenic response of rat femoral small arteries in relation to wall structure and [Ca(2+)](i)

The present study investigated the influence of media thickness on myogenic tone and intracellular calcium concentration ([Ca(2+)](i)) in rat skeletal muscle small arteries. A ligature was loosely tied around one external iliac artery of 5-wk-old spontaneously hypertensive rats. At 18 wk of age, femoral artery blood pressure was 102 +/- 11 mmHg (n = 15) on the ligated side and 164 +/- 6 mmHg (n = 15) on the contralateral side. Small arteries feeding the gracilis muscle had a reduced media cross-sectional area and a reduced media-to-lumen ratio on the ligated side, where also the range of myogenic constriction was shifted to lower pressures. However, when expressed as a function of wall stress, diameter responses were nearly identical. [Ca(2+)](i) was higher in vessels from the ligated hindlimb at pressures above 10 mmHg, but vasoconstriction was not accompanied by changes in [Ca(2+)](i). Thus the myogenic constriction here seems due primarily to changes in intracellular calcium sensitivity, which are determined mainly by the force per cross-sectional area of the wall and therefore altered by changes in vascular structure.     

Decrease in endothelium-dependent relaxation in the mesenteric arterial bed following vascular calcium overload produced by vitamin D3 and nicotine in rats.

Treatment of young rats with vitamin D3 plus nicotine, which has been proposed as a model of cardiovascular calcium overload, produced an increase in the calcium content of the mesenteric arterial bed and lowered in vitro vasoconstrictor responses to norepinephrine and serotonin. Attenuation of the vasoconstriction induced by norepinephrine by the endothelium-dependent vasodilators, carbachol and histamine, was diminished, but the effects of sodium nitroprusside and papaverine were unchanged. The vitamin D3 plus nicotine model may be useful for the study of the involvement of calcium overload in vascular endothelial dysfunction.     

Abnormal magnesium metabolism in two rat models of genetic hypertension.

Magnesium concentrations in erythrocyte ghosts and arterial tissue of male, spontaneously hypertensive rats (SHR) were significantly less than in these tissues of male normotensive controls (Wistar-Kyoto; WKY) of the same age, which were also fed rat chow and tap water. The magnesium concentration in SHR erythrocyte ghosts was increased to the control value by incubating SHR erythrocytes with WKY blood plasma; SHR plasma did not affect the magnesium concentration in WKY erythrocyte ghosts. The magnesium concentrations in erythrocyte ghosts, aortas, and mesenteric arteries from female salt-sensitive (SS/JR) and salt-resistant (SR/JR) Dahl-derived rats, both maintained ad libitum on laboratory rat chow and either tap water or 0.9% NaCl, were not different but were significantly less than those of Sprague-Dawley rats considered as controls. While the ingestion of 0.9% NaCl had no effect on the magnesium concentrations measured in these animals, it caused the salt-sensitive rats to become severely hypertensive. It is evident from these observations that the decreased binding of magnesium to the plasma membrane of cells may be an inheritable metabolic defect that may be associated with the development of hypertension. However, in those instances of hypertension in which this defect occurs, it appears to be a contributing cause of the hypertension; by itself the defect is not a cause of hypertension.     

Changes of heme oxygenase-carbon monoxide system in vascular calcification in rats

The aim of the present study was to investigate the change in heme oxygenase (HO)-carbon monoxide (CO)-cyclic guanosine monophosphate (cGMP) pathway in vascular calcification. Vascular calcification model was established in rats by using vitamin D(3) and nicotine. Vascular calcium content, alkaline phosphatase (ALP) activity, HO activity, HbCO formation and content of cGMP in vessels were measured. Immunochemistry (IH) for HO 1 expression and in situ hybridization (ISH) for HO 1 mRNA were observed. Compared to those of control rats, the aortic calcium content and vascular ALP activity in rats of the calcified group (VDN group) were obviously increased, but HO 1 activity, CO concentration and cGMP content in vessels of rats in VDN group were markedly decreased. Expressions of HO-1 protein and mRNA were significantly decreased compared to control rats. Vascular calcification might induce a down regulation in vascular HO-CO-cGMP pathway.     

Sensitivity and adrenoceptor affinity in the mesenteric artery of the deoxycorticosterone acetate hypertensive rat

This study examines vascular reactivity to alpha-adrenoceptor agonists in mineralocorticoid (deoxycorticosterone acetate (DOCA-salt) hypertensive and normotensive rats. The rats were anesthetized and the mesenteric artery was excised and cut helically into strips that were mounted in a muscle bath for the measurement of isometric force development. Addition of norepinephrine, epinephrine, phenylephrine, methoxamine, or clonidine to the bath caused contractions in all arteries. Arteries from hypertensive rats were more sensitive (lower ED50 values) to each of the agonists than arteries from normotensive rats. alpha-Adrenoceptor affinity for phentolamine (Schild analysis; norepinephrine as the agonist) in hypertensive arteries was not significantly different from that in normotensive arteries. Maximal force generation to clonidine was greater in hypertensive arteries than in normotensive arteries. These results demonstrate an augmented vascular sensitivity to several alpha-adrenoceptor agonists in DOCA hypertensive rats. This change in sensitivity is independent of a change in affinity for the adrenoceptor antagonist, phentolamine. It may be that a change in receptor number or an alteration in a post-receptor activation event accounts for this enhanced adrenoceptor responsiveness in mineralocorticoid hypertension.     

Vascular responses to sodium arachidonate in experimental hypertension

This study characterizes vascular responsiveness to sodium arachidonate (C 20:4) in four models of hypertension [deoxycorticosterone acetate (DOCA) hypertensive rats, two kidney-one clip (2K-1C) renal hypertensive rats, spontaneously hypertensive rats (SHR), and psychosocial hypertensive mice]. Isolated arterial strips (aorta, mesenteric artery, tail artery) were equilibrated under optimal resting tension in physiological salt solution for measurement of isometric force generation. Dose-response curves to arachidonate (10(-10) to 10(-4) g/ml) in arteries from DOCA and 2K-1C hypertensive rats were shifted to the left compared to those in arteries from control rats. In arteries from SHR and psychosocial hypertensive mice, the dose-response relationships were unchanged compared to normotensive values. Arteries from DOCA hypertensive and 2K-1C hypertensive rats developed greater maximal contractile responses to arachidonate than controls; maximal responses in arteries from SHR and psychosocial hypertensive mice were unchanged compared to normotensive values. Contractions to arachidonate were inhibited by indomethacin (0.5 and 5 micrograms/ml) and by aspirin (5 and 50 micrograms/ml). The fatty acid, oleate (C 18:1), had no effect on the contractile state of the arteries, whereas prostaglandin F2 alpha caused contraction. These results indicate altered responsiveness to exogenous arachidonate in arteries from DOCA and 2K-1C hypertensive rats, but not in arteries from SHR and psychosocial hypertensive mice.     

Chronic hypoxia augments protein kinase G-mediated Ca2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling

Pulmonary vascular smooth muscle (VSM) sensitivity to nitric oxide (NO) is enhanced in pulmonary arteries from rats exposed to chronic hypoxia (CH) compared with controls. Furthermore, in contrast to control arteries, relaxation to NO following CH is not reliant on a decrease in VSM intracellular free calcium ([Ca(2+)](i)). We hypothesized that enhanced NO-dependent pulmonary vasodilation following CH is a function of VSM myofilament Ca(2+) desensitization via inhibition of the RhoA/Rho kinase (ROK) pathway. To test this hypothesis, we compared the ability of the NO donor, spermine NONOate, to reverse VSM tone generated by UTP, the ROK agonist sphingosylphosphorylcholine, or the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate in Ca(2+)-permeabilized, endothelium-denuded pulmonary arteries (150- to 300-microm inner diameter) from control and CH (4 wk at 0.5 atm) rats. Arteries were loaded with fura-2 AM to continuously monitor VSM [Ca(2+)](i). We further examined effects of NO on levels of GTP-bound RhoA and ROK membrane translocation as indexes of enzyme activity in arteries from each group. We found that spermine NONOate reversed Y-27632-sensitive Ca(2+) sensitization and inhibited both RhoA and ROK activity in vessels from CH rats but not control animals. In contrast, spermine NONOate was without effect on PKC-mediated vasoconstriction in either group. We conclude that CH mediates a shift in NO signaling to promote pulmonary VSM Ca(2+) desensitization through inhibition of RhoA/ROK.     

Effects of homocysteine on intracellular nitric oxide and superoxide levels in the renal arterial endothelium

The present study was designed to test the hypothesis that homocysteine (Hcys) reduces intracellular nitric oxide (NO) concentrations ([NO](i)) and stimulates superoxide (O.) production in the renal arterial endothelium, thereby resulting in endothelial dysfunction. With the use of fluorescence microscopic imaging analysis, a calcium ionophore, A-23187 (2 microM), and bradykinin (2 microM) were found to increase endothelial [NO](i) in freshly dissected lumen-opened small renal arteries loaded with 4,5-diaminofluorescein diacetate (DAF-2DA; 10 microM). Preincubation of the arteries with L-Hcys (20-40 microM) significantly attenuated the increase in endothelial [NO](i). However, L-Hcys had no effect on NO synthase activity in the renal arteries, as measured by the conversion rate of [(3)H]arginine to [(3)H]citrulline, but it concentration dependently decreased DAF-2DA-sensitive fluorescence induced by PAPA-NONOate in the solution, suggesting that L-Hcys reduces endothelial [NO](i) by its scavenging action. Because other thiol compounds such as L-cysteine and glutathione were also found to reduce [NO](i), it seems that decreased NO is not the only mechanism resulting in endothelial dysfunction or arteriosclerosis in hyperhomocysteinemia (hHcys). By analysis of intracellular O. levels using dihydroethidium trapping, we found that only L-Hcys among the thiol compounds studied markedly increased O. levels in the renal endothelium. These results indicate that L-Hcys inhibits the agonist-induced NO increase but stimulates O. production within endothelial cells. These effects of L-Hcys on [NO](i) and [O.] may contribute to endothelial injury associated with hHcys.     

Ionic permeability and blood pressure

The difficulty of establishing a causal relationship between any measured phenomenon and hypertension is emphasized. The literature concerning ion movements in tissues from hypertensive patients and animals is briefly reviewed. It is pointed out that the evidence (i) is conflicting concerning changes of permeability of red blood cells in patients with hypertension; (ii) is more consistent in leukocytes; and (iii) is virtually nonexistent regarding ionic permeability of blood vessels from man. A few studies suggest that permeability to calcium is altered in aortae from hypertensive animals and that concentrations of calcium in platelets are correlated with blood pressure in man. Some of our previously published work on red blood cells is then summarized which suggests that altered passive permeability to calcium exists in red blood cells from spontaneously hypertensive rats. Experiments are described using the calcium antagonists D-600 or felodipine to further study previously reported differences in calcium handling in blood vessels from spontaneously hypertensive rats. We could detect no difference in the effects of these calcium antagonists on blood vessels from hypertensive animals compared with controls. It is suggested that the finding of increased passive permeability to calcium in tissues from hypertensive animals is a lead worth pursuing.     

Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage

Arteries that develop vasospasm after subarachnoid hemorrhage (SAH) may have altered contractility and compliance. Whether these changes are due to alterations in the smooth muscle cells or the arterial wall extracellular matrix is unknown. This study elucidated the location of such changes and determined the calcium sensitivity of vasospastic arteries. Dogs were placed under general anesthesia and underwent creation of SAH using the double-hemorrhage model. Vasospasm was assessed by angiography performed before and 4, 7, or 21 days after SAH. Basilar arteries were excised from SAH or control dogs (n = 8-52 arterial rings from 2-9 dogs per measurement) and studied under isometric tension in vitro before and after permeabilization of smooth muscle with alpha-toxin. Endothelium was removed from all arteries. Vasospastic arteries demonstrated significantly reduced contractility to KCl with a shift in the EC(50) toward reduced sensitivity to KCl 4 and 7 days after SAH (P < 0.05, ANOVA). There was reduced compliance that persisted after permeabilization (P < 0.05, ANOVA). Calcium sensitivity was decreased during vasospasm 4 and 7 days after SAH, as assessed in permeabilized arteries and in those contracted with BAY K 8644 in the presence of different concentrations of extracellular calcium (P < 0.05, ANOVA). Depolymerization of actin with cytochalasin D abolished contractions to KCl but failed to alter arterial compliance. In conclusion, it is shown for the first time that calcium sensitivity is decreased during vasospasm after SAH in dogs, suggesting that other mechanisms are involved in maintaining the contraction. Reduced compliance seems to be due to an alteration in the arterial wall extracellullar matrix rather than the smooth muscle cells themselves because it cannot be alleviated by depolymerization of smooth muscle actin.     

Pressure-dependent myogenic constriction of cerebral arteries occurs independently of voltage-dependent activation

Pressure-induced decreases in arterial diameter are accompanied by membrane depolarization and Ca(2+) entry via voltage-gated Ca(2+) channels. Recent evidence also suggests the involvement of Ca(2+) sensitization of the contractile proteins. Both PKC and Rho kinase are candidate second messengers for the mediation of the sensitization process. We investigated the signaling pathways of pressure-induced decreases in rat cerebral artery diameter in vessels that were depolarized with a 60 mM potassium-physiological salt solution (KPSS). Arteries were mounted on a pressure myograph, and pressure-induced constrictions were recorded. In some experiments simultaneous changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) were recorded by using fura 2 fluorescence photometry. Pressure increases induced constriction with significant changes in [Ca(2+)](i) at high pressures (60-100 mmHg). The ratio of the change in diameter to change in [Ca(2+)](i) was greater for pressure-induced constriction compared with constriction produced by depolarization with 60 mM KPSS, suggesting that in addition to increases in [Ca(2+)](i), enhanced myofilament Ca(2+) sensitivity occurs during pressure-induced decreases in arterial diameter. Depolarizing the membrane with 60 mM KPSS increased [Ca(2+)](i) via a Ca(2+) influx pathway insensitive to PKC inhibition. Cerebral arteries were able to maintain their diameters in the continued presence of 60 mM KPSS. Pressure-induced constriction under these conditions was not associated with further increases in Ca(2+) but was abolished by selective inhibitors of PLC, PKC, and Rho kinase. We report for the first time that in rat cerebral arteries, pressure-induced decreases in arterial diameter are not only due to increases in voltage-gated Ca(2+) influx but also to accompanying increases in myofilament sensitivity to Ca(2+) mediated by PKC/Rho kinase activation.     

Arterial blood pressure and high calcium diet in normal and mineralcorticoid (DOCA and sodium chloride hypertensive rats]

High calcium diet induces an hypertension lasting one week in normal rats. In mineralocorticoid treated rats (DOCA + NaCl), the same diet prevents for 10 weeks the increase of arterial blood pressure. Parathyroid activity (estimated by urinary cAMP) is decreased after the high calcium diet. These results confirm the role of the parathyroid glands in mineralocorticoid hypertension in the rat.