Changes in vascular responsiveness following chronic exposure to cold in the rat

The responsiveness of smooth muscle from rings of aortic tissue of cold-acclimated (CA, 6 degrees C, 5-15 wk) rats to both alpha- and beta-adrenergic agonists and KCl was tested and compared with that of warm-adapted (25 degrees C) controls. alpha-Adrenergic stimulation, induced by low doses (10(-8)-10(-7) M) of phenylephrine and norepinephrine in the presence and absence of the beta-adrenergic antagonist, propranolol, resulted in the development of less active tension by aortic smooth muscle from CA rats than from controls. Similar results were observed with the weakly alpha 1-adrenergic agonistic activities of tyramine, clonidine, and high concentrations of isoproterenol (10(-6)-10(-4) M). There was also a significant reduction in the tension developed by smooth muscles of the aortas from CA rats when depolarized with KCl in concentrations ranging from 8 to 20 mM. In contrast, aortic smooth muscle, contracted to 75% of maximum with KCl, showed an enhanced relaxation to the beta-adrenergic agonist, isoproterenol, in CA rats. These studies suggest that acclimation of rats to cold results in both a decrease in alpha-adrenergic responsiveness and an increase in beta-adrenergic responsiveness in vascular smooth muscle as well as a change in the biochemical events that couple activation of adrenergic receptors to changes in vasomotor tone.     

Effect of vitamin A deficiency on cardiovascular function in the rat

Selected parameters of cardiovascular function were evaluated in vitamin A-deficient rats at 70 days of age. Resting heart rate was increased by an average of 100 bpm (21.4+/-2.7%), whereas resting systolic blood pressure was normal in vitamin A-deficient animals. The maximal contractile force developed per milligram weight of tissue by aortic rings excised from vitamin A-deficient animals was reduced in response to high potassium (-25.0+/-8.7%) and phorbol 12,13-dibutyrate (-36.8+/-8.4%) but was only slightly reduced in response to norepinephrine (-17.8+/-11.1%). Intimal rubbing to remove the endothelium had no effect on the loss in contractile responsiveness, and the relaxant response to acetylcholine was similar between control and vitamin A-deficient tissue groups. This suggests that the decrease in contractility of vascular smooth muscle from the vitamin A-deficient rats did not involve altered release of endothelium-derived vasoactive factors. Western blot analysis suggested a reduction in the protein levels of several differentiation markers including alpha-actin (-22%), calponin (-37%), desmin (-37%), and vinculin (-40%), whereas the level of PKCalpha was unchanged from control values. Our findings indicate a significant decrease in contractile responsiveness of aortic smooth muscle of the vitamin A-deficient rat that may be associated with a down regulation in the expression of contractile-related proteins.     

Antibodies against AT1 Receptors Are Associated with Vascular Endothelial and Smooth Muscle Function Impairment: Protective Effects of Hydroxysafflor Yellow A

Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA) are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165–191) to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day) and hyroxysafflor yellow A (HSYA) (10 mg/kg/day). The result show that systolic blood pressure (SBP) and heart rate (HR) of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells.     

Smooth Muscle LDL Receptor-Related Protein-1 Deletion Induces Aortic Insufficiency and Promotes Vascular Cardiomyopathy in Mice

Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1) in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.     

Cerebral intraventricular 6-hydroxydopamine prevents vascular changes in the mineralocorticoid hypertensive rat

The effect of cerebral intraventricular administration of 6-hydroxydopamine (6-OHDA) on blood pressure and vascular smooth muscle responsiveness in deoxycorticosterone acetate (DOCA)-treated rats was assessed. Rats treated with 6-OHDA and DOCA had significantly lower systolic blood pressures (142 +/- 8 mm Hg) than rats treated with DOCA alone (185 +/- 5 mm Hg). After 5 weeks of DOCA treatment, femoral arteries and aortae were excised from these rats, cut helically into strips, and placed in a muscle bath to record isometric force. Dose-response curves to serotonin were shifted to the left in femoral arteries from DOCA-treated rats compared to both control and 6-OHDA-DOCA-treated rats (ED50: DOCA = 6.8 X 10(-8) M, control = 27.9 X 10(-8) M, 6-OHDA-DOCA = 13.4 X 10(-8) M). Arachidonic acid, the prostaglandin precursor, produced greater maximal contractions in femoral artery strips of DOCA-treated rats (358 +/- 56 mg) than in those from controls (115 +/- 31 mg). The maximal response to arachidonic acid in arteries from 6-OHDA-DOCA rats (203 +/- 78 mg) was not different from control values. Ouabain produced a greater maximal response in aortic strips from DOCA rats (658 +/- 165 mg) compared to those from control (196 +/- 72 mg) or 6-OHDA-DOCA (309 +/- 87 mg) rats. We conclude that increased vascular responsiveness to serotonin, arachidonic acid, and ouabain in DOCA hypertensive rats is secondary to a central action of the mineralocorticoid.     

Increased arterial potassium transport in reduced renal mass hypertension of the rat

Aortic potassium turnover was studied during the development of hypertension induced by salt load in male rats after 70-75% of total renal mass was removed. Systolic blood pressure in the saline-drinking experimental reduced renal mass (RRM) rats steadily increased until the fourth week after surgery and thereafter stayed at the same level. Control RRM rats given tap water for drinking, and unilaterally nephrectomized saline-drinking control rats maintained normal blood pressure. Compared to controls, experimental RRM rats exhibited increased plasma aldosterone concentration while plasma renin activity was low in all groups with no significant difference. Aortic hypertrophy, greater 42K turnover, and elevated 42K exchange were observed with experimental RRM hypertension. Sensitivity to the effect of norepinephrine (NE) on aortic 42K turnover was increased four- to ninefold in the experimental RRM group as compared to controls. These results indicate that reduced renal mass hypertension is associated with increased potassium permeability and NE supersensitivity in vascular smooth muscle.     

Hemodynamic effects of nicotine in canine skeletal muscle.

Studies were conducted in 36 artificially ventilated, anesthetized dogs to clarify hemodynamic effects of nicotine in resting gracilis muscle. In Series 1, effects of intravenous nicotine (36 micrograms/kg/min) were evaluated in (i) intact muscles (Condition 1), (ii) denervated muscles (Condition 2), (iii) denervated muscles following local alpha-adrenergic blockade (Condition 3), (iv) denervated muscles following combined local alpha- and beta-adrenergic blockade (Condition 4), and (v) intact muscles with aortic pressure maintained constant (Condition 5). In Series 2, nicotine was infused directly into the gracilis artery at a rate of 3.6 micrograms/kg/min. Muscle blood flow was obtained with an electromagnetic flowmeter and used to calculate vascular resistance and oxygen consumption (Fick equation). Plasma catecholamine levels were determined with a radioenzymatic method. Intravenous nicotine doubled mean aortic pressure under Conditions 1-4. In intact and denervated muscles (Conditions 1 and 2) proportional increases in vascular resistance, reflective of vasoconstriction, held blood flow constant. Muscle oxygen consumption was unchanged. alpha-Adrenergic blockade with phenoxybenzamine following denervation (Condition 3) converted muscle vasoconstriction to vasodilation during nicotine infusion. Additional beta-adrenergic blockade (Condition 4) restored muscle vasoconstriction. Nicotine-induced muscle vasoconstriction was maintained under controlled pressure (Condition 5). Intravenous nicotine significantly increased plasma catecholamine levels. Intra-arterial infusions of nicotine (Series 2) caused no hemodynamic changes in muscle. In conclusion, intravenous nicotine caused vasoconstriction in muscle, which was not due to reduced metabolic demand, pressure-flow autoregulation, or a direct [corrected] effect on vascular smooth muscle, but to stimulation of alpha-adrenergic receptors. Following denervation, this vasoconstriction was maintained by elevated plasma catecholamines. alpha-Adrenergic blockade unmasked nicotine-induced vasodilation mediated by beta-adrenergic receptors, whereas combined alpha- and beta-adrenergic blockade unmasked nicotine-induced vasoconstriction by a nonadrenergic mechanism.     

Angiotensin II-induced hypertrophy is potentiated in mice overexpressing p22phox in vascular smooth muscle

Increased reactive oxygen species (ROS) are implicated in several vascular pathologies associated with vascular smooth muscle hypertrophy. In the current studies, we utilized transgenic (Tg) mice (Tg(p22smc)) that overexpress the p22(phox) subunit of NAD(P)H oxidase selectively in smooth muscle. These mice have a twofold increase in aortic p22(phox) expression and H(2)O(2) production and thus provide an excellent in vivo model in which to assess the effects of increased ROS generation on vascular smooth muscle cell (VSMC) function. We tested the hypothesis that overexpression of VSMC p22(phox) potentiates angiotensin II (ANG II)-induced vascular hypertrophy. Male Tg(p22smc) mice and negative littermate controls were infused with either ANG II or saline for 13 days. Baseline blood pressure was not different between control and Tg(p22smc) mice. ANG II significantly increased blood pressure in both groups, with this increase being slightly exacerbated in the Tg(p22smc) mice. Baseline aortic wall thickness and cross-sectional wall area were not different between control and Tg(p22smc) mice. Importantly, the ANG II-induced increase in both parameters was significantly greater in the Tg(p22smc) mice compared with control mice. To confirm that this potentiation of vascular hypertrophy was due to increased ROS levels, additional groups of mice were coinfused with ebselen. This treatment prevented the exacerbation of hypertrophy in Tg(p22smc) mice receiving ANG II. These data suggest that although increased availability of NAD(P)H oxidase-derived ROS is not a sufficient stimulus for hypertrophy, it does potentiate ANG II-induced vascular hypertrophy, making ROS an excellent target for intervention aimed at reducing medial thickening in vivo.     

罗格列酮对胰岛素抵抗高血压大鼠主动脉功能的影响

为探讨罗格列酮(rosiglitazone,ROSI)对胰岛素抵抗高血压大鼠(insulin resistant-hypertensive rats,IRHR)主动脉功能的影响及其可能机制,用高果糖饲养Sprague-Dawley大鼠8周,制备IRHR模型,并通过相关指标的检测判断造模是否成功。随后采用血管环灌流方法,观察各实验组动物离体胸主动脉环对新福林(L-phenylephrine,PE)、氯化钾(KCl)的收缩反应和对乙酰胆碱(acetylcholine,ACh)、硝普钠(sodium nitroprusside,SNP)的舒张反应：以及用一氧化氮合酶(nitric oxide synthase,NOS)的抑制剂N-硝基-L-精氨酸甲酯(N^ω-nitro-L-arginine methyl ester,L-NAME)预孵育血管30min后,主动脉环对ACh的舒张反应：同时对各实验组血清一氧化氮(nitric oxide,NO)的含量进行测定。结果显示：(1)罗格列酮能降低IRHR的收缩压、血清胰岛素水平,改善胰岛素抵抗。(2)高果糖组动物主动脉对PE、KCl的收缩反应明显增强,对ACh的舒张反应明显减弱,ROSI可逆转上述作用。(3)用L-NAME预处理后,高果糖组动物主动脉对ACh的舒张反应进一步减弱,ROSI可部分对抗上述作用。(4)各组大鼠离体主动脉对SNP的舒张反应无显著性差异。(5)ROSI对对照组大鼠主动脉功能的影响不明显。(6)与对照组相比,高果糖组动物血清NO含量显著降低,用ROSI处理后,血清NO含量显著增加。上述结果表明,ROSI能改善IRHR主动脉的舒张功能,其作用的机制可能是部分通过NOS途径促进内皮NO释放,或是通过降低血压、血清胰岛素水平,以及改善胰岛素抵抗等作用,导致血管舒张。     

Blood pressure regulates the activity and function of the Na-K-2Cl cotransporter in vascular smooth muscle

The Na-K-2Cl cotransporter (NKCC1) is one of several transporters that have been linked to hypertension, and its inhibition reduces vascular smooth muscle tone and blood pressure. NKCC1 in the rat aorta is stimulated by vasoconstrictors and inhibited by nitrovasodilators, and this is linked to the contractile state of the smooth muscle. To determine whether blood pressure also regulates NKCC1, we examined the acute effect of hypertension on NKCC1 in rats after aortic coarctation. In the hypertensive aorta (28-mmHg rise in mean blood pressure), an increase in NKCC1 activity (measured as bumetanide-sensitive (86)Rb efflux) was apparent by 16 h and reached a plateau of 62% greater than control at 48 h. In contrast, there was a slight decrease in NKCC1 activity in the hypotensive aorta (21% decrease in mean blood pressure). Measurement of NKCC1 mRNA by real-time PCR revealed a fivefold increase in the hypertensive aorta compared with the hypotensive aorta or sham aorta. The inhibition by bumetanide of isometric force response to phenylephrine was significantly greater in the hypertensive aorta than in the control aorta or hypotensive aorta. We conclude that NKCC1 in rat aortic smooth muscle is regulated by blood pressure, most likely through changes in transporter abundance. This upregulation of NKCC1 is associated with a greater contribution to force generation in the hypertensive aorta. This is the first demonstration that NKCC1 in vascular smooth muscle is regulated by blood pressure and indicates that this transporter is important in the acute response of vascular smooth muscle to hypertension.     

Comparison of the effect of simvastatin, spironolactone and L-arginine on endothelial function of aorta in hereditary hypertriglyceridemic rats

Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endothelium-dependent relaxation of conduit arteries. The aim of this study was to investigate the effect of long-term (4 weeks) treatment of hHTG rats with three drugs which, according to their mechanism of action, may be able to modify the endothelial function: simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase), spironolactone (an antagonist of aldosterone receptors) and L-arginine (a precursor of nitric oxide formation). At the end of fourth week the systolic blood pressure in the control hHTG group was 148+/-2 mm Hg and in control normotensive Wistar group 117+/-3 mm Hg. L-arginine failed to reduce blood pressure, but simvastatin (118+/-1 mm Hg) and spironolactone (124+/-4 mm Hg) treatment significantly decreased the systolic blood pressure. In isolated phenylephrine-precontracted aortic rings from hHTG rats endothelium-dependent relaxation was diminished as compared to control Wistar rats. Of the three drugs used, only simvastatin improved acetylcholine-induced relaxation of the aorta. We conclude that both simvastatin and spironolactone reduced blood pressure but only simvastatin significantly improved endothelial dysfunction of aorta. Prominent increase in the expression of eNOS in large conduit arteries may be the pathophysiological mechanism underlying the protective effect of simvastatin in hHTG rats.     

Impact of vitamin D3 on cardiovascular responses to glucocorticoid excess

Although the cardiovascular system is not a classical target for 1,25-dihydroxyvitamin D₃, both cardiac myocytes and vascular smooth muscle cells respond to this hormone. The present study aimed to elucidate the effect of active vitamin D₃ on cardiovascular functions in rats exposed to glucocorticoid excess. Adult male Wistar rats were allocated into three groups: control group, dexamethasone (Dex)-treated group receiving Dex (200 μg/kg) subcutaneously for 12 days, and vitamin D₃-Dex-treated group receiving 1,25-(OH)₂D₃ (100 ng/kg) and Dex (200 μg/kg) subcutaneously for 12 days. Rats were subjected to measurement of systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures and heart rate. Rate pressure product (RPP) was calculated. Rats’ isolated hearts were perfused in Langendorff preparation and studied for basal activities (heart rate, peaked developed tension, time to peak tension, half relaxation time, and myocardial flow rate) and their responses to isoproterenol infusion. Blood samples were collected for determination of plasma level of nitrite, nitric oxide surrogate. Dex-treated group showed significant increase in SBP, DBP, MAP, and RPP, as well as cardiac hypertrophy and enhancement of basal cardiac performance evidenced by increased heart rate, rapid and increased contractility, and accelerated lusitropy, together with impaired contractile and myocardial flow rate responsiveness to beta-adrenergic activation and depressed inotropic and coronary vascular reserves. Such alterations were accompanied by low plasma nitrite. These changes were markedly improved by vitamin D₃ treatment. In conclusion, vitamin D₃ is an efficacious modulator of the deleterious cardiovascular responses induced by glucocorticoid excess, probably via accentuation of nitric oxide.     

Potassium turnover and norepinephrine sensitivity in the thoracic aorta of the Dahl rat

This in vitro study evaluated the basal 42K turnover and response to norepinephrine (NE) in the thoracic aorta removed from Dahl salt-sensitive (S) and salt-resistant (R) rats. Five-week-old S and R rats were placed on either a high-salt (HS) or low-salt (LS) diet. After 5 weeks of the diet, systolic blood pressure, aortic weight/length ratio, and the cellular pool of K+ were elevated in the S-HS group only. In contrast, the steady state turnover of 42K, the NE ED50, and the response to a supramaximal dose of NE were the same in both groups of salt-sensitive and salt-resistant rats. These results suggest that, despite the presence of a greatly elevated systolic blood pressure and evidence of aortic hypertrophy, the intrinsic electrolyte metabolism of the vascular smooth muscle in the Dahl hypertensive rat is the same as that of the Dahl normotensive rat.     

Differential cerebrovascular responsiveness in spontaneously hypertensive rats following antihypertensive treatment with clonidine and verapamil

Numerous studies have been reported examining the effects of antihypertensive treatment on peripheral vascular responsiveness in spontaneously hypertensive rats (SHR). This study was conducted to determine the effects of chronic treatment with 2 antihypertensive agents on cerebrovascular responsiveness in male SHR and Wistar-Kyoto (WKY) rats. SHR and WKY (3–4 weeks old) received either placebo, clonidine (CLON, 10 mg pellet) or verapamil (VER, 5 mg pellet). Vascular reactivity studies on the basilar artery, using standard smooth muscle bath techniques, were conducted following 6 weeks of treatment. Both CLON and VER significantly attenuated the rise in blood pressure in SHR. Basilar artery responsiveness to KCl, serotonin (5-HT), and calcium were significantly increased whereas responses to acetylcholine (ACH), isoproterenol (ISO) and sodium nitroprusside (SNP) were significantly reduced in SHR compared to WKY. CLON had no effect on basilar artery responsiveness to either the contractile or relaxation agents in SHR. However, although responses to KCl, 5-HT and calcium were not affected by VER in SHR, VER significantly increased the responses to ACH, ISO and SNP. Neither CLON nor VER treatment affected basilar artery responsiveness to any of the agents in WKY. These data demonstrate that, even though CLON and VER have similar antihypertensive effects, differential effects of the 2 agents on cerebrovascular responsiveness in the SHR are apparent. This would suggest that the vascular effects of VER and CLON are dependent upon the mechanism of action of the agents and not simply due to prevention of the elevation in blood pressure.     

4-苯基丁酸抑制内质网应激改善高同型半胱氨酸引起的血管重构

摘要 目的：探讨高同型半胱氨酸血症（hyperhomocysteinemia, HHcy）导致血管损伤的机制并证明内质网应激抑制剂4-苯基丁酸（4-PBA）在其中的保护作用。方法：采用蛋氨酸饲料喂养SD大鼠制备HHcy模型,24只大鼠随机分为3组（每组8只）：对照组（Control）、HHcy模型组（HHcy）和4-PBA处理组（4-PBA）;测量大鼠血压和心率,检测血清中同型半胱氨酸浓度,HE染色观察血管形态,Western blot和免疫组化染色观察内质网应激分子GRP78和GRP94的表达,Western blot检测内质网应激促凋亡因子CHOP和Caspase 12的表达,TUNEL染色观察主动脉血管的细胞凋亡。结果：3组大鼠血压和心率没有显著差异（P>0.05）;和Control组比较,HHcy组血清中同型半胱氨酸浓度明显增加（P<0.05）,而4-PBA处理组血清同型半胱氨酸浓度与HHcy组比有降低但没有统计学差异（P>0.05）;和Control组比较,HHcy组主动脉血管平滑肌细胞肥大,走行紊乱,部分断裂,细胞核固缩,管壁增厚,内质网应激分子GRP78和GRP94以及促凋亡因子CHOP和Caspase 12的表达明显增加（P<0.05）,TUNEL染色阳性细胞也显著增多;而4-PBA处理组能明显改善HHcy组主动脉血管的这些变化（P<0.05）。结论：高同型半胱氨酸血症能引起主动脉血管重构,而4-PBA可通过抑制内质网应激和细胞凋亡改善高同型半胱氨酸血症引起的血管重构。     

生物反馈联合电刺激在女性盆底功能障碍性疾病治疗中的临床应用

目的:分析生物反馈联合电刺激对女性盆底功能障碍性疾病(PFD)的治疗效果。方法:选择2011年1月至2016年3月我院收治的1000例PFD患者为研究对象,按随机数字表法分为实验组和对照组,每组各500例。实验组给予生物反馈联合电刺激,对照组给予功能性电刺激治疗。比较两组治疗前后盆底肌肉肌力分级的变化,测定盆底功能相关指标的改善及患者治疗前后排尿情况。结果:治疗后2组盆底肌力分级均呈明显上升趋势(Z=52.587,37.581;P0.001),且观察组改善效果优于对照组(Z=27.588,P0.001);治疗后实验组盆底肌肉肌力正常率高于对照组,差异有统计学意义(x~2=68.323,P0.05);治疗后实验组最大收缩压、持续收缩压提升幅度较大,膀胱颈移动度明显减小,与对照组各项指标对比差异有统计学意义(P0.05),且治疗后两组排尿情况均有所好转,实验组效果优于对照组(P0.05)。结论:生物反馈联合电刺激对女性PFD具有较好的效果,能提高患者盆底最大收缩压、持续收缩压,减小膀胱颈移动度,改善患者排尿功能。     

Reactivity of rat abdominal aorta to U46619 following whole-body gamma irradiation

Rats exposed to 20 Gy whole-body irradiation demonstrated a depressed aortic responsiveness to the thromboxane mimic, U46619, 48 h postirradiation. The mechanism for this observed response was investigated. Shielding the abdominal aorta attenuated this altered vascular reactivity. Since this suggests that radiation exposure induces local changes in the aorta, vascular smooth muscle function was assessed with cumulative concentrations of KCl. Radiation-induced smooth muscle damage was insufficient to account for the decreased reactivity to U46619. Next, calcium availability for vascular smooth muscle function was evaluated and found not to be responsible for the radiation-induced depression in aortic responsiveness. Finally, the role that cyclooxygenase products play in the depressed contractile response was investigated. Indomethacin treatment prior to and for 48 h after irradiation attenuated the altered vascular reactivity to U46619. These data suggest that a radiation-induced increase in cyclooxygenase products may play a role in the decreased aortic reactivity to the thromboxane mimic.     

Smooth muscle relaxation and local hydraulic impedance properties of the aorta.

Smooth muscle relaxation is expected to yield beneficial effects on hydraulic impedance properties of large vessels. We investigated the effects of intravenous diltiazem infusion on aortic wall stiffness and local hydraulic impedance properties. In seven anesthetized, closed-chest dogs, instantaneous cross-sectional area and pressure of the descending thoracic aorta were measured using transesophageal echocardiography combined with acoustic quantification and a micromanometer, respectively. Data were acquired during a vena caval balloon inflation, both at the control condition and with diltiazem infusion. At the operating point, diltiazem reduced blood pressure in all dogs but did not alter aortic dimensions or wall stiffness. Over the observed pressure range, aortic area-pressure relationships were linear. Whereas diltiazem affected the slope of this relationship variably (no change in 3 dogs, increase in 1 dog, decrease in 3 dogs), the zero-pressure area intercept was significantly increased in every case such that higher area was observed at any given pressure. When comparisons were made at a common level of wall stress, wall stiffness was either increased or unchanged during diltiazem infusion. In contrast, diltiazem decreased wall stiffness in every case when comparisons were made at a common level of aortic midwall radius. Aortic characteristic impedance and pulse wave velocity, components of left ventricular hydraulic load that are determined by aortic elastic and geometric properties, were affected variably. A comparison of wall stiffness at matched wall stress appears inappropriate for assessing changes in smooth muscle tone. Because of the competing effects of changes in vessel diameter and wall stiffness, smooth muscle relaxation is not necessarily accompanied by the expected beneficial changes in local aortic hydraulic impedance. These results can be reconciled by recognizing that components other than vascular smooth muscle (e.g., elastin, collagen) contribute to aortic wall stiffness.     

Dietary vitamin C supplementation lowers blood pressure in spontaneously hypertensive rats

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca²⁺ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. Vitamin C can increase tissue cysteine and glutathione levels. The aim of the present study was to investigate whether a dietary supplementation of vitamin C can lower tissue aldehydes and blood pressure and normalize associated biochemical and histopathological changes in SHRs. Starting at 12 weeks of age, animals were divided into 3 groups of 6 animals each. Animals in the WKY-control group and SHR-control group were given a normal diet and the SHR-vitamin C group a diet supplemented with vitamin C (1000 mg/kg feed) for the next 9 weeks. After nine weeks, systolic blood pressure, platelet [Ca²⁺]_i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared to WKY controls and the SHR-vitamin C group. SHR-controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin C supplementation in SHRs lowered the systolic blood pressure, tissue aldehyde conjugates and attenuated adverse renal vascular changes.     

Reduction of blood pressure by indirect biofeedback

Forty-five randomly assigned subjects served in either a relaxation control, an EMG plus thermal, or a thermal biofeedback group. All groups received the same relaxation manipulation. Experimental results demonstrated a significant drop in both diastolic and systolic blood pressure for the feedback treatment. Diastolic measures showed a somewhat greater decrease for the EMG plus thermal treatment condition. A learning effect was demonstrated both within and across the three experimental sessions. Given that the sample was normotensive, the 20% reduction in blood pressure was notable. The results support the idea that blood pressure biofeedback is not a necessary condition for reduction of arterial blood pressure.