In vivo PIV measurement of red blood cell velocity field in microvessels considering mesentery motion

As endothelial cells are subject to flow shear stress, it is important to determine the detailed velocity distribution in microvessels in the study of mechanical interactions between blood and endothelium. Recently, particle image velocimetry (PIV) has been proposed as a quantitative method of measuring velocity fields instantaneously in experimental fluid mechanics. The authors have developed a highly accurate PIV technique with improved dynamic range. spatial resolution and measurement accuracy. In this paper, the proposed method was applied to images of the arteriole in the rat mesentery using an intravital microscope and high-speed digital video system. Taking the mesentery motion into account, the PIV technique was improved to measure red blood cell (RBC) velocity. Velocity distributions with spatial resolutions of 0.8 x 0.8 microm were obtained even near the wall in the centre plane of the arteriole. The arteriole velocity profile was blunt in the centre region of the vessel cross-section and sharp in the near-wall region. Typical flow features for non-Newtonian fluid were shown. Time-averaged velocity profiles in six cross sections with different diameters were compared.     

Decreased supply-dependent oxygen consumption in the skeletal muscle of the spontaneously hypertensive rat during acute hypoxia

The purpose of this study was to correlate microvascular oxygen delivery (DO2) and consumption (VO2) in the skeletal muscle of spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKY) with hemodynamics during acute hypoxia. We expected greater abnormalities in central and microvascular hemodynamics during hypoxic induced shock in the SHR compared with the WKY due to microvascular rarefaction. The inspired oxygen fraction (FiO2) was lowered from 0.21 to 0.15, 0.1, 0.08, and 0.05 in anesthetized, mechanically ventilated rats. Lactate and base deficit values were similar for both groups at 0.21 and 0.15 FiO2, but higher in SHR at lower FiO2. Baseline aortic blood flow (SHR, 56.2+/-4.0 mL min; WKY, 61.8+/-5.3 mL min) and systemic DO2 (SHR, 9.02+/-0.82 mL min; WKY, 9.32+/-0.54 mL min) increased similarly when FiO2 was lowered to 0.15. Further reductions in FiO2 caused lower aortic flow and systemic DO2 in the SHR than WKY at 0.08 and 0.05 FiO2. Spinotrapezius blood flow increased from baseline (SHR, 24.8+/-1.8 nL s; WKY, 22.7+/-2.1 nL s) in both groups when FiO2 was reduced to 0.15; further reductions in FiO2 decreased blood flow in both groups, with lower values in the SHR group at 0.1 and 0.08 FiO2. The SHR group demonstrated higher venous oxygen saturation at low values of FiO2 compared with WKY. This reduced oxygen extraction in SHR resulted in a lower supply-dependent VO2 at low values of spinotrapezius DO2, perhaps attributed to arteriolar thickening and rarefaction seen in chronic hypertension.     

Spatiotemporal processing in photoplethysmography for skin microcirculatory perfusion imaging

Technological advances in the real-time visualization of cutaneous microcirculation aim to realize benefits including high-resolution imaging, suppressed noise, and robust temporal coherence. Photoplethysmography (PPG), a noninvasive technique that measures single or multiple points of relative blood volume changes in blood vessels under the skin, shows potential as a signal candidate for visualizing blood vessels and tracking blood flow. However, challenges still remain, such as extracting/image reconstruction of the blood vessel/flow signal in a precise frequency window (<0.2 Hz) from a noisy image that is caused by the loss of spatial coherence of the light source in a turbid biological tissue. We attempted to overcome this challenge by adopting a combination of direct-contact-type, lens-less, conformable imagers and singular value decomposition (SVD) in this study. We focused on the numerical analysis of SVD for discriminating the tissue and vein blood flow in PPG for reconstructing blood fluidic images, followed by a complete demonstration of skin microcirculation blood tracking in the vessel visualization process when applying our lens-less, conformable, wearable imagers.     

Genetic co-segregation of renal haemodynamics and blood pressure in the spontaneously hypertensive rat

1. To determine the relevance of renal circulatory abnormalities found in the immature spontaneously hypertensive rat (SHR) to the genetic hypertensive process, glomerular filtration rate and renal blood flow were measured in conscious F2 rats, derived from cross-breeding SHR and normotensive Wistar-Kyoto rats (WKY), at 4, 11 and 16 weeks of age by determining the renal clearances of 51Cr-ethylenediaminetetra-acetate and 125I-hippuran respectively. Plasma renin activity was measured at 11 and 16 weeks of age. 2. Mean arterial pressure, glomerular filtration rate and renal blood flow increased between 4 and 11 weeks of age. Between 11 and 16 weeks the mean glomerular filtration rate and renal blood flow did not alter, although the mean arterial pressure rose significantly. At 11 weeks of age, during the developmental phase of hypertension, a significant negative correlation between mean arterial pressure and both glomerular filtration rate and renal blood flow was noted. However, by 16 weeks when the manifestations of genetic hypertension were more fully expressed, no correlation between mean arterial pressure and renal blood flow or glomerular filtration rate was observed. Plasma renin activity was negatively correlated with both glomerular filtration rate and renal blood flow, but the relationship was stronger at 11 than at 16 weeks of age. 3. These results suggest that the reduction in renal blood flow and glomerular filtration rate, found in immature SHR, is genetically linked to the hypertension and may be of primary pathogenetic importance. It is proposed that the increased renal vascular resistance in these young animals stimulates the rise of systemic arterial pressure which returns renal blood flow and glomerular filtration rate to normal.     

Heparin lowers blood pressure and vascular calcium uptake in hypertensive rats

Increased calcium uptake by vascular tissue, leading to elevated cytosolic calcium, has been implicated in the pathophysiology of hypertension. Heparin treatment of hypertensive rats has been known to lower blood pressure but its mechanism is not known. This study examined the effect of chronic heparin treatment on systolic blood pressure, aortic calcium and 87Rubidium (86Rb) uptake of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Starting at 12 weeks of age SHR and WKY rats were given either sodium heparin 300 units s.c. or equal amounts of saline once a day for a period of 6 weeks. At 18 weeks, systolic blood pressure, uptakes of calcium and 86Rb by aortae were significantly higher (p less than 0.01) in saline-treated SHR compared with heparin-treated SHR and WKY. Heparin treatment lowered the elevated calcium and 86Rb Uptake and blood pressure in SHR but had no effect on WKY. The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in SHR. Heparin appears to lower elevated blood pressure in SHR by lowering elevated vascular calcium uptake.     

Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats

OBJECTIVES: We tested the following hypotheses: a) spontaneously hypertensive stroke-prone rats (SHR-SP) have more brain injury than spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) when exposed to transient focal ischemia; b) infarction size is not correlated with baseline blood pressure; and c) infarction size is inversely related to the cerebral hyperemic response to oxotremorine, a muscarinic agonist that increases cerebral blood flow (CBF) by stimulating endothelial nitric oxide synthase. DESIGN: In vivo study. SETTING: Animal laboratory in a university teaching hospital. SUBJECTS: Adult age-matched male WKY, SHR, and SHR-SP. INTERVENTIONS: Rats were instrumented under halothane anesthesia. Transient focal cerebral ischemia was produced for 2 hrs with the intravascular suture technique. Cerebral perfusion, estimated with laser Doppler flowmetry (LD-CBF), in response to intravenous oxotremorine, was measured in one cohort of rats to estimate endothelial nitric oxide synthase function. Infarction volume was measured at 22 hrs of reperfusion with 2,3,5-triphenyltetrazolium chloride staining. MEASUREMENTS AND MAIN RESULTS: Infarction volume in the striatum of SHR-SP (42+/-4 mm3) was greater than in SHR (29+/-6 mm3) or WKY (1+/-1 mm3) (n = 9 rats/strain). Resting (unanesthetized) mean arterial blood pressure was similar in SHR-SP (177+/-5 mm Hg) and SHR (170+/-5 mm Hg) despite a greater infarction volume in SHR-SP (n = 4) compared with SHR (n = 5). The percentage increase in LD-CBF signal in response to oxotremorine was similar for both groups (SHR, 64%+/-22% [n = 10]; SHR-SP, 69%+/-22% [n = 8]). However, in this cohort, cortical infarction volume was less in SHR (30%+/-4% of ipsilateral cortex) than in SHR-SP (49%+/-2% of ipsilateral cortex). CONCLUSIONS: Although SHR-SP have greater infarction volume than SHR, the mechanism of injury does not appear to be related to a difference in unanesthetized baseline mean arterial blood pressure or to an alteration in endothelium-produced nitric oxide.     

Inhibition of Rho-kinase reduces renal Na-H exchanger activity and causes natriuresis in rat

Rho-kinase regulates the actin cytoskeleton and therefore modulates transport. The role of Rho-kinase in Na-H exchanger (NHE) activity of rat proximal convoluted tubules (PCTs) was investigated using (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632), a specific inhibitor of Rho-kinase. In spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, apical and basolateral NHE activities were determined by measuring cell pH recovery following luminal NH4+ prepulse and basolateral sodium removal, respectively. Apical NHE activity was greater in 8 to 9 week old hypertensive SHR compared with WKY. Although Y-27632 suppressed pH(i) recovery in both strains, sensitivity was 50-fold higher in adult SHR. Y-27632 suppressed basolateral NHE in both strains with similar sensitivity. Apical NHE activity was not greater in 5-week-old, not yet hypertensive, SHR rats compared with WKY. In clearance studies, Na excretion was less in SHR than in WKY rats. Y-27632 increased Na excretion and fractional excretion Na in both strains but more so in SHR. (22)Na uptake of the brush border membrane vesicle taken from Y-27632-treated rats decreased more than that from vehicle-treated animals in both adult SHR and WKY. We conclude that apical NHE activity is increased in SHR PCT compared with controls and that inhibition of Rho-kinase reduces PCT NHE activities and causes natriuresis.     

Decreased membrane fluidity of erythrocytes and cultured vascular smooth muscle cells in spontaneously hypertensive rats: an electron spin resonance study

1. Membrane fluidity of erythrocytes and cultured vascular smooth muscle cells was studied in spontaneously hypertensive rats (SHR; Okamoto and Aoki strains) by means of an electron spin resonance (e.s.r.) and a spin-label technique. 2. The values of outer hyperfine splitting (2T') and of the order parameter (S) determined from e.s.r. spectra for a fatty acid spin-label agent (5-nitroxy stearate) were significantly higher in erythrocytes of SHR (4 and 10-13 weeks of age) than in those of age-matched Wistar-Kyoto rats (WKY). This finding suggests that the membrane fluidity of erythrocytes might be decreased in SHR. 3. The fluidity of cultured vascular smooth muscle cells obtained from 10-13-week-old SHR was also reduced compared with that from WKY. 4. These results suggest that the decreased membrane fluidity might be a genetically determined abnormality of the cell membranes in SHR.     

Leukotriene D4: cardiovascular and sympathetic effects in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats

Leukotriene D4 (1--20 micrograms/kg i.a.) administered to conscious spontaneously hypertensive rats (SHR) and WKY rats caused acute elevation of blood pressure in both groups, but only in SHR a prolonged hypotensive period followed the hypertensive event. SHR rats had tachycardia during the hypertensive phase and relative bradycardia during the hypotensive phase which was more pronounced and prolonged than in WKY rats. In SHR rats only, plasma epinephrine and norepinephrine were elevated (6- and 3-fold, respectively) at the peak of the hypertensive period. Pretreatment of SHR rats with indomethacin (5 mg/kg) potentiated the LTD4-induced pressor response and shortened the hypotensive-bradycardic effect of LTD4. This same biphasic, dose-dependent response to LTD4 (1--20 micrograms/kg i.v.) was present in pithed SHR rats. Therefore, a direct action of LTD4 on vascular smooth muscle and heart is suggested. In all WKY rats and some SHR rats, a bradycardic effect of LTD4 resulted from sinus bradycardia, whereas in pithed SHR rats impaired conduction varying from transient second degree atrioventricular block to complete heart block was observed. Electrocardiographic signs of ischemia were seen only in LTD4-injected, pithed SHR rats. These results suggest fundamental differences between SHR and WKY rats in regard to their sensitivity to lipoxygenase products.     

Endothelial regulation of cyclic GMP and vascular responses in hypertension

The mechanism whereby endothelial modulation of drug-induced vascular responses might change during hypertension was examined. Acetylcholine (ACh) (1 microM) induced maximal relaxation of aortic ring segments with intact endothelium from both Wistar-Kyoto, normotensive rats (WKY) and spontaneously hypertensive rats (SHR) at 5 to 6 weeks of age. At 15 to 18 weeks of age the relaxation response to ACh was reduced in rings from both SHR and WKY (to a greater extent in SHR) and was attenuated even more in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. The contractile responses of aortic preparations to norepinephrine (NE) (0.1 microM) were similar between 5-6-week-old and 15-18-week-old WKY, but were increased in 15-18-week-old SHR compared to 5-6-week-old SHR. Endothelial cell removal increased contractile responses to NE to a greater extent in WKY than SHR but this did not affect that seen in DOCA-salt hypertensive rats. Methylene blue treatment increased contractions of aortic rings with intact endothelium from 15-18-week-old WKY and SHR to the level detected in rubbed arteries, but it did not affect the NE-induced constriction of intact aortic rings from DOCA-salt hypertensive rats. Basal cyclic GMP concentrations in intact aortic rings were not different between SHR and WKY at 5 to 6 weeks of age. The basal aortic cyclic GMP was unchanged in WKY at 15 to 18 weeks of age, but decreased in SHR and in DOCA-salt hypertensive rats of the same age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Errors in measuring blood flow velocity behind hepatic mass lesions using color doppler sonography

The authors designed microcomputer simulation models to investigate the combined effect of a distorted grayscale ultrasound image and an inaccurately measured Doppler angle on the accuracy of measurement of blood-flow velocity in vessels located behind mass lesions in the liver. Error decreased when flow was measured at the midpoint of the posttumoral segment of the vessel and increased with distance between the mass and the vessel, with inclination of the vessel, and with decrease in the diameter of the mass. Error was least with the sector probe, intermediate with the convex probe, and greatest with the linear probe. These findings suggest that the error can be minimized when measuring blood flow velocity in a vessel located behind a mass, if the Doppler images are acquired using a sector probe from the midpoint of the posttumoral segment of the vessel.     

Disturbance of acid-base balance in the young spontaneously hypertensive rat

1. The acid-base status of young spontaneously hypertensive rats (SHR) was compared with that of Wistar-Kyoto rats (WKY) in the steady state, after acid loading and after blood pressure had been maintained at normal levels from weaning. Whole blood ionized calcium was measured simultaneously. 2. In the prehypertensive stage (4 weeks of age), plasma bicarbonate was significantly lower in SHR than in WKY, while blood pH did not differ significantly. 3. After 6 weeks of age, blood pH and plasma bicarbonate were significantly lower in both anaesthetized and conscious SHR than in corresponding WKY. After 7 days administration of NH4Cl in the drinking fluid, both parameters decreased significantly in both strains and the difference in pH remained constant (0.05 pH unit, P less than 0.01). 4. In none of the groups investigated did non-pH-adjusted ionized calcium differ significantly between the SHR and WKY. 5. Prevention of the development of hypertension in SHR by hydralazine treatment from weaning did not increase pH or bicarbonate compared with untreated SHR, indicating that the metabolic acidosis in the SHR was not a consequence of raised blood pressure. 6. Disturbance in acid-base balance may be involved in the pathogenesis of raised blood pressure in this animal model of genetic hypertension.     

alpha 2-Adrenoceptors potentiate angiotensin II- and vasopressin-induced renal vasoconstriction in spontaneously hypertensive rats

Hypertension in spontaneously hypertensive rats (SHRs) is due in part to enhanced effects of vasoactive peptides on the renal vasculature. We hypothesize that the G(i) signal transduction pathway enhances renovascular responses to vasoactive peptides in SHRs more so than in normotensive Wistar-Kyoto (WKY) rats. To test this hypothesis, we examined in isolated perfused kidneys from SHRs and WKY rats the renovascular responses (assessed as changes in renal perfusion pressure in mm Hg) to angiotensin II (10 nM) and vasopressin (3 nM) in the presence and absence of UK-14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine; an agonist that selectively activates the G(i) pathway by stimulating alpha(2)-adrenoceptors]. In SHR, but not WKY, kidneys, UK-14,304 (10 nM) enhanced (P < 0.05) renovascular responses to angiotensin II (control WKY, 43 +/- 6; UK-14,304-treated WKY, 52 +/- 19; control SHR, 66 +/- 17; UK-14,304-treated SHR, 125 +/- 16) and vasopressin (control WKY, 42 +/- 17; UK-14,304-treated WKY, 36 +/- 11; control SHR, 16 +/- 8; UK-14,304-treated SHR, 83 +/- 17). Pretreatment of SHRs with pertussis toxin (30 microg/kg, intravenously, 3-4 days before study) to inactivate G(i) blocked the effects of UK-14,304. Western blot analysis of receptor expression in whole kidney and preglomerular microvessels revealed similar levels of expression of AT(1), V(1a), and alpha(2A) receptors in SHRs compared with WKY rats. We conclude that activation of alpha(2)-adrenoceptors selectively enhances renovascular responses to angiotensin II and vasopressin in SHRs via an enhanced cross talk between the G(i) signal transduction pathway and signal transduction pathways activated by angiotensin II and vasopressin.     

超声评价非诺贝特对自发性高血压大鼠心肌重构的干预作用

目的 应用超声技术评价非诺贝特对自发性高血压大鼠心肌重构的影响。方法 自发性高血压大鼠（spontaneous hypertensive rats，SHR）22只随机分为SHR用药组（12只）和SHR未用药组（10只），同周龄Wistar—kyoto（WKY）大鼠10只作为正常对照。非诺贝特治疗8周，分别于实验前后进行超声心动图检查，8周末处死动物进行组织学检查。结果实验后，与WKY组相比，SHR未用药组室壁厚度、左室相对质量显著增加（P＜0．01），二尖瓣口血流流速曲线E／A值明显减小（P＜0．01），E峰减速时间明显延长（P＜0．05）；SHR用药组与SHR未用药组相比以上指标均有明显改善（P＜0．05）。SHR未用药组室间隔、左室后壁的平均声学强度（AID、心包校正的声学强度明显增高（P＜0．01），峰一峰强度明显降低（P＜0．01）；SHR用药组与SHR未用药组相比以上声学密度指标均有明显改善（P＜0．05）。超声所计算的左室相对质量与实体标本测值具有较高的相关性（r=0．729，P＜0．001）。结论 非诺贝特具有干预SHR心肌重构的作用，声学密度技术结合常规超声心动图能较全面、准确评价此作用。     

Cytoplasmic free [Ca2+] is increased in the platelets of spontaneously hypertensive rats and essential hypertensive patients

The cytoplasmic free calcium concentration [( Ca2+]i) was assessed with the fluorescent dye Quin 2 in platelets and lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), essential hypertensive patients (EHP) and normotensive human control subjects (NCS). [Ca2+]i was significantly higher in the platelets of 8- and 20-week-old SHR in comparison with WKY. However, no difference was evident after weaning. Changes of cellular calcium in hypertensive rats apparently evolved simultaneously with the development of high arterial pressure. [Ca2+]i was significantly higher in platelets of EHP than in NCS. In lymphocytes of SHR, [Ca2+]i was not different from WKY at 4 and 8 weeks, but was increased at 14 weeks and at older ages. In EHP, intralymphocytic [Ca2+] was only modestly higher than in controls. On the whole, the results suggest that control of cytoplasmic calcium in these blood cells is similarly affected in human and animal models of primary hypertension.     

Velocity measurement accuracy in optical microhemodynamics: experiment and simulation

Micro particle image velocimetry (μPIV) is a common method to assess flow behavior in blood microvessels in vitro as well as in vivo. The use of red blood cells (RBCs) as tracer particles, as generally considered in vivo, creates a large depth of correlation (DOC), even as large as the vessel itself, which decreases the accuracy of the method. The limitations of μPIV for blood flow measurements based on RBC tracking still have to be evaluated. In this study, in vitro and in silico models were used to understand the effect of the DOC on blood flow measurements using μPIV RBC tracer particles. We therefore employed a μPIV technique to assess blood flow in a 15?μm radius glass tube with a high-speed CMOS camera. The tube was perfused with a sample of 40% hematocrit blood. The flow measured by a cross-correlating speckle tracking technique was compared to the flow rate of the pump. In addition, a three-dimensional mechanical RBC-flow model was used to simulate optical moving speckle at 20% and 40% hematocrits, in 15 and 20?μm radius circular tubes, at different focus planes, flow rates and for various velocity profile shapes. The velocity profiles extracted from the simulated pictures were compared with good agreement with the corresponding velocity profiles implemented in the mechanical model. The flow rates from both the in vitro flow phantom and the mathematical model were accurately measured with less than 10% errors. Simulation results demonstrated that the hematocrit (paired t tests, p = 0.5) and the tube radius (p = 0.1) do not influence the precision of the measured flow rate, whereas the shape of the velocity profile (p < 0.001) and the location of the focus plane (p < 0.001) do, as indicated by measured errors ranging from 3% to 97%. In conclusion, the use of RBCs as tracer particles makes a large DOC and affects the image processing required to estimate the flow velocities. We found that the current μPIV method is acceptable to estimate the flow rate on the condition that the measurement takes place at the equatorial plane of the vessel. Otherwise, it is not an appropriate method to estimate the shape of the velocity profile.     

Defective modulation of noradrenergic neurotransmission by endogenous prostaglandins in aging spontaneously hypertensive rats

Sympathetic nerve stimulation causes a greater vascular response in spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto normotensive rats (WKY), i.e., noradrenergic neurotransmission is enhanced in SHR. Prejunctional and/or postjunctional defects in the regulation of noradrenergic neurotransmission by endogenous prostaglandins could contribute to the increased responsiveness to sympathetic nerve stimulation in SHR. This hypothesis was tested by comparing the effects in SHR vs. WKY of inhibition of cyclooxygenase on vascular responses to periarterial nerve stimulation (PNS), norepinephrine (NE) and angiotensin II (ang II) in the in situ blood perfused rat mesentery. The cyclooxygenase inhibitor, indomethacin, potentiated vascular responses to PNS and NE similarly in 16-week old SHR vs. age-matched WKY. However, in this age group, indomethacin enhanced responses to ang II more in SHR compared with WKY. To determine whether chronic exposure of the vasculature to high blood pressure might alter the physiological significance of prostaglandin-mediated regulation of noradrenergic neurotransmission in vivo, additional studies were conducted in SHR and WKY that were 25 weeks old. In this age group, neither indomethacin nor ibuprofen, an alternative cyclooxygenase inhibitor, significantly potentiated responses to either PNS or NE in SHR, whereas in WKY both indomethacin and ibuprofen potentiated responses to PNS and NE. Also, in these older animals, indomethacin and ibuprofen enhanced responses to ang II equally in SHR vs. WKY. These findings indicate that in aging SHR prostaglandin-mediated regulation of vascular responses to sympathetic nerve stimulation becomes defective. This defect may contribute to the worsening of high blood pressure with age and may be involved in some of the vascular pathology associated with hypertension.     

Phorbol-12,13-dibutyrate-induced vasoconstriction in vivo: characterization of response in genetic hypertension

To assess the role of protein kinase C (PKC) in the control of vessel tone in vivo in genetic hypertension, the vascular effects of phorbol-12,13-dibutyrate (PDBu), a PKC activator, was measured in the autoperfused hindlimb of reserpinized spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). PDBu infusion (1-3000 ng/kg/min) into the hindlimb elevated perfusion pressure in a dose-related manner. Vasoconstriction response characteristics (latency, T1/2 to peak effect, decay of effect) of PDBu were significantly longer (2- to 10-fold) than that produced by membrane receptor agonists; phenylephrine, SKF 89748, a lipophilic alpha-1 agonist, angiotensin II and 5-hydroxytryptamine. The tonic vasoconstriction induced by PDBu was not antagonized by prazosin, rauwolscine, cyproheptadine, [Sar1lle8]-angiotensin II but was inhibited reversibly by microbial PKC-inhibitors, K252a and staurosporine at concentrations (1.56-2.8 micrograms/kg/min) which did not block vasoconstriction by phenylephrine or 5-hydroxytryptamine. The EC50 for PDBu was identical in SHR and WKY. However, the maximal response to PDBu was significantly greater in SHR compared to WKY. Staurosporine lowered mean arterial pressure equally in SHR (20%) and WKY (17%) but reduced perfusion pressure in SHR (13%) to a slightly greater extent than in WKY (5%). Unlike the in vivo response, aortic rings removed from SHR were more sensitive to cumulative doses of PDBu than rings from WKY. It is concluded that PDBu-vasoconstriction in vivo is mediated largely through activation of PKC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct and acute cardiotoxic effects of ultrafine air pollutants in spontaneously hypertensive rats and Wistar--Kyoto rats

It is hypothesized that preexisting cardiovascular disease could affect the susceptibility to direct and acute cardiotoxic effects of ultrafine air pollutants. Ultrafine particles (UFP) isolated from 12.5 mg of diesel particulate matter (National Institute of Standards and Technology) were infused into isolated Langendorffperfused hearts obtained from spontaneously hypertensive rats (SHR) and normotensive control Wistar- Kyoto rats (WKY). Perfusion for 30 minutes with UFP reduced cardiac function in both groups-but to a greater extent in WKY. In SHR, developed pressure was reduced by 24.1 +/- 4.4% of baseline and maximal dP/dt was reduced by 19.8 +/- 4.9%; in WKY, developed pressure was reduced by 43.5 +/- 7.3% and maximal dP/dt by 41.8 +/- 8.2% (P < .05 for maximal dP/dt in SHR vs WKY). Coronary flow was decreased by 30.3% versus 53.7% in SHR versus WKY ( P < .05). The results of this study suggest that although UFP depress myocardial contractile response and coronary flow in both SHR and WKY the underlying hypertension does not necessarily worsen the response.     

Hypotensive and diuretic actions of diltiazem in spontaneously hypertensive and Wistar Kyoto rats

We investigated the hypotensive and diuretic effects of diltiazem and hydralazine in conscious, spontaneously hypertensive rats (SHR) and their counterpart, Wistar Kyoto rats (WKY). Orally administered diltiazem induced dose-dependent hypotension both in SHR (10-60 mg/kg) and in WKY (30-100 mg/kg) and the effects were more pronounced in SHR than in WKY. Diltiazem did not cause tachycardia in either strain. Moreover, hypotensive doses of diltiazem acutely increased urinary excretion of sodium as well as urine volume in saline-loaded SHR and WKY. Chronic administration of diltiazem (30 mg/kg/day for 8 weeks) to young SHR caused no changes in body fluid distribution or in plasma sodium concentration. On the other hand, hydralazine not only showed almost the same hypotensive potency in SHR and WKY but also resulted reflex tachycardia in both strains. In addition, hydralazine (5 mg/kg) decreased urinary sodium excretion in saline-loaded SHR. In conclusion, it was suggested that diltiazem is an antihypertensive agent with an enhanced hypotensive action in the hypertensive state and without tachycardia and sodium retention effects.