Assessment of the vasoactive effects of the (S)-epimers of ergot alkaloids in vitro.

Ergot alkaloids are produced by the fungus Claviceps purpurea and their levels are carefully monitored in animal and human diets due to their harmful effects and widespread contamination of cereal crops. Ergot alkaloids exist in two forms known as the (R)- and (S)-epimers with only the former being monitored in diets in North America. The (S)-epimers of ergot alkaloids are thought to be biologically inactive and, therefore, harmless. A major mechanism by which the (R)-epimers of ergot alkaloids produce their toxic effect is through vasoconstriction. Therefore, the objective of this study was to examine the vasoactivity potential (contractile response) of four (S)-epimers, namely ergocryptinine, ergocristinine, ergocorninine, and ergotaminine utilizing an in vitro arterial tissue bath system. Bovine metatarsal arteries (n = 6, ergocryptinine and ergocorninine; n = 6, ergocristinine and ergotaminine; n = 6 arteries/(S)-epimer, total n = 12) were collected from healthy mixed-breed beef steers immediately after slaughter, cut into 3-mm arterial cross sections, and suspended in a tissue bath with continuously oxygenated Krebs-Henseleit buffer. To assess the contractile response of each (S)-epimer, a cumulative contractile dose-response curve was constructed by incubating arteries with increasing concentrations (1 × 10-11 to 1 × 10-6 M) of that (S)-epimer. Contractile responses were recorded as grams of tension and were normalized to an initial contraction of phenylephrine. Contrary to the widespread belief, all tested (S)-epimers were found vasoactive and produced a concentration-dependent arterial contractile response similar to what has been reported for the (R)-epimers. The arterial contractile response to ergotaminine was strongest and was significantly greater than that of ergocryptinine and ergocristinine at the highest concentration used (P ≤ 0.01). Our results indicate that the (S)-epimers are biologically active and are likely harmful similar to the (R)-epimers. The levels of (S)-epimers should be carefully monitored in human and animal diets worldwide.

Synthesis and assessment of sodium alginate-modified silk fibroin microspheres as potential hepatic arterial embolization agent.

Transcatheter arterial chemoembolization (TACE) is well known as an effective treatment for hepatocellular carcinoma (HCC). In the present study, a novel embolic agent of sodium alginate (SA)-modified silk fibroin (SF) microspheres was successfully prepared by emulsifying cross-linking method. The SA-modified SF microspheres were evaluated for the ability of embolization by investigating the morphology, particle size, swelling ratio, degradation, cytotoxicity, blood compatibility, and in vivo embolization. The results found that SA-modified SF microspheres had smooth surfaces and good sphericity. Swelling ratio of the microspheres can meet the requirements of arterial embolic agent and have pH and temperature sensitivity. Furthermore, hemolytic and anticoagulant studies have proved that the microspheres have good blood compatibility. Cytotoxicity tests indicated that the microspheres could promote the proliferation of fibroblasts and HUVEC. In vivo embolization evaluation of microspheres revealed that the arteries could be embolized by SA-modified SF microspheres in 3 weeks. The ability of drug loading and releasing of microspheres was proved by the controlled release profile of Adriamycin hydrochloride. The findings indicated that the SA-modified SF microspheres can be used as a potentially biodegradable arterial embolic agent for liver cancer therapy.

Overview of results from the Vitamin D Assessment (ViDA) study.

BACKGROUND: The Vitamin D Assessment (ViDA) study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy of monthly vitamin D supplementation in reducing the incidence of a range of acute and chronic diseases and intermediate outcomes. METHODS: The study was carried out in Auckland, New Zealand, among 5110 adults, aged 50-84 years, who were followed for a median 3.3 years. The intervention was vitamin D3 (2.5 mg or 100,000 IU) or placebo softgel oral capsules, mailed monthly to participants' homes, with two capsules sent in the first mail-out post-randomisation (i.e. 200,000 IU bolus, or placebo), followed 1 month later (and thereafter monthly) with 100,000 IU vitamin D3 or placebo capsules. Outcomes were monitored through routinely collected health data and self-completed questionnaires. RESULTS: The results showed no beneficial effect of vitamin D supplementation on incidence of cardiovascular disease, falls, non-vertebral fractures and all cancer. However, beneficial effects from vitamin D supplementation were seen: for persistence with taking statins in participants on long-term statin therapy; and also in bone mineral density and arterial function in participants with low 25-hydroxyvitamin D levels, and in lung function among ever smokers (especially if vitamin D deficient). The latter findings are consistent with several previous studies, CONCLUSION: Monthly high-dose vitamin D supplementation does not prevent a range of diseases, but may be beneficial for some intermediate outcomes in people who are vitamin D deficient. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry identifier: ACTRN12611000402943.

New insights into arterial stiffening: does sex matter?

This review discusses sexual dimorphism in arterial stiffening, disease pathology interactions, and the influence of sex on mechanisms and pathways. Arterial stiffness predicts cardiovascular mortality independent of blood pressure. Patients with increased arterial stiffness have a 48% higher risk for developing cardiovascular disease. Like other cardiovascular pathologies, arterial stiffness is sexually dimorphic. Young women have lower stiffness than aged-matched men, but this sex difference reverses during normal aging. Estrogen therapy does not attenuate progressive stiffening in postmenopausal women, indicating that currently prescribed drugs do not confer protection. Although remodeling of large arteries is a protective adaptation to higher wall stress, arterial stiffening increases afterload to the left ventricle and transmits higher pulsatile pressure to smaller arteries and target organs. Moreover, an increase in aortic stiffness may precede or exacerbate hypertension, particularly during aging. Additional studies are needed to elucidate the mechanisms by which females are protected from arterial stiffness to provide insight into its mechanisms and, ultimately, therapeutic targets for treating this pathology.

Assessment of impaired vascular reactivity in a rat model of diabetic nephropathy: effect of nitric oxide synthesis inhibition on intrarenal diffusion and oxygenation measured by magnetic resonance imaging.

Diabetes is associated with impaired vascular reactivity and the development of diabetic nephropathy. In a rat model of streptozotocin-induced diabetic nephropathy, the effects of systemic nitric oxide (NO) synthesis inhibition on intrarenal diffusion and oxygenation were determined by noninvasive magnetic resonance diffusion tensor imaging and blood O2 level-dependent (BOLD) imaging, respectively. Eight weeks after the induction of diabetes, 21 rats [n = 7 rats each in the untreated control group, diabetes mellitus (DM) group, and DM with uninephrectomy (DM UNX) group] were examined by MRI. Diffusion tensor imaging and BOLD sequences were acquired before and after NO synthesis inhibition with N-nitro-L-arginine methyl ester (L-NAME). In the same rats, mean arterial pressure and vascular conductance were determined with and without the influence of L-NAME. In control animals, NO synthesis inhibition was associated with a significant increase of mean arterial pressure of 33.8 ± 4.3 mmHg (P < 0.001) and a decrease of vascular conductance of -17.8 ± 2.0 µl·min(-1)·100 mmHg(-1) (P < 0.001). These changes were attenuated in both DM and DM UNX groups with no significant difference between before and after L-NAME measurements in DM UNX animals. Similarly, L-NAME challenge induced a significant reduction of renal transverse relaxation time (T2*) at MRI in control animals, indicating reduced renal oxygenation after L-NAME injection compared with baseline. DM UNX animals did not show a significant T2* reduction after NO synthesis inhibition in the renal cortex and attenuated T2* reduction in the outer medulla. MRI parameters of tissue diffusion were not affected by L-NAME in all groups. In conclusion, BOLD imaging proved valuable to noninvasively measure renal vascular reactivity upon NO synthesis inhibition in control animals and to detect impaired vascular reactivity in animals with diabetic nephropathy.

[State of the structure and functions of the arterial wall in patients with chronic heart failure against the background of permanent atrial fibrillation and assessment of vasoprotective effect of omega-3 polyunsaturated fatty acids].

PURPOSE: to evaluate the state of the structure and function of the arterial wall in patients with chronic heart failure (CHF) of ischemic etiology in combination with persistent atrial fibrillation (AF) AF and the dynamics of their changes during therapy with omega-3 polyunsaturated fatty acids (omega-3 PUFA). MATERIAL AND METHODS: in the first phase in order to identify characteristics of a CCF and the restructuring of the arterial wall 120 patients with coronary artery disease and chronic heart failure II-III functional class (FC) were included in the study, then were divided into two equal groups according to the presence of persistent AF. In the second phase patients with CHF and persistent AF were randomized into 2 groups of 30 people to determine the vasoprotective effect of omega-3 fatty acids compared with the standard treatment of CHF. The duration of treatment was 6 months. To assess the conductive and damping functions of arteries comprehensive sfigmopletizmografiyu was carried out. To assess the state of the arteries collagen matrix we determined the level of tissue inhibitor of matrix metalloproteinases type I (TIMP-1) by enzyme immunoassay. RESULTS: in patients with chronic heart failure of ischemic etiology in combination with persistent AF we revealed more severe functional impairment of the arterial wall, characterized by an increase in pulse wave velocity in carotid-femoral segment (p=0.037), the aorta (p<0.001), indexes CAVI1 (p less or equal 0.001) and augmentation (p=0.049; p<0.001) in the absence of differences in the group of patients with heart failure and sinus rhythm in terms of structural changes in collagen matrix- TIMP-1. The progress of CHF against the background persistent AF was characterized by higher levels of atrial natriuretic peptide with prevalence of diastolic dysfunction, while the more frequent co-morbidities (hypertension, diabetes mellitus type 2, stroke/transient ischemic attack), and risk factors. Inclusion in the treatment of patients with chronic heart failure of ischemic etiology and persistent AF omega-3 fatty acids provides reliable vasoprotective effect by suppressing the abnormal collagen formation on the dynamics of TIMP-1 (p<0.001) and improving the elastic properties of the arterial wall to the dynamics of high-speed data and indexed blood flow the arterial tree (p<0.001), with the exception of ankle-brachial indexes. CONCLUSION: structurally functional remodeling of the arterial wall in patients with chronic heart failure of ischemic etiology and persistent AF has a definite pattern of forming. Omega-3 fatty acids have a vasoprotective effect, providing improving elastic properties of the arteries by preventing fibrosis.

The influence of tocolytic drugs on cardiac function, large arteries, and resistance vessels.

PURPOSE: Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs, but are associated with cardiovascular side-effects. Atosiban, a newer drug, is a competitive antagonist of oxytocin and has been claimed to have fewer cardiovascular side effects. Until now, there has mainly been a subjective reporting of adverse reactions and few objective cardiovascular data. Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban compared with placebo on cardiac function, large artery properties, blood pressure, and resistance vessels. METHODS: A double-blind, randomized trial was carried out in 20 non-pregnant female volunteers. Hemodynamic measurements were made under standardized conditions during kinetic steady state. Cardiac output was measured with echocardiography, large artery properties with an echo-tracking device. The effect on the microcirculation was estimated using the total peripheral resistance index (TPRI). RESULTS: Atosiban did not differ from placebo. With ritodrine, cardiac function increased by 79% compared with placebo because of a rise in heart rate (91%). TPRI decreased by 48%. Ritodrine increased the distensibility of the common carotid artery by 62% and the compliance by 83%, independent of blood pressure. Compliance of the common femoral artery increased independently of pressure by 33% and the distensibility by 59%. Aortic pulse wave velocity was not influenced by either medication. CONCLUSIONS: The present study shows potential beneficial vascular effects of ritodrine that are counterbalanced by the cardiac effects. Atosiban has no clinically relevant cardiovascular effects and may be a good alternative for ritodrine in pregnant women at risk of cardiovascular complications.

Assessment of arterial stiffness affected by atorvastatin in coronary artery disease using pulse wave velocity.

PURPOSE: Several studies have shown arterial stiffness changes associated with coronary artery disease (CAD). Recently, statins were reported to improve arterial stiffness. The aim of the study was to evaluate the effect of atorvastatin on arterial stiffness in CAD patients using pulse wave velocity (PWV). METHODS: We evaluated 63 patients with hyperlipemia and CAD. Forty-three patients were given 10mg atorvastatin daily and 20 patients were assigned to a low-fat diet. Carotid-femoral PWV (PWV-CF), carotid-radial PWV (PWV-CR) and carotid-distal PWV (PWV-CD) were measured in all patients. RESULTS: Compared with baseline, PWV-CF, PWV-CR and PWV-CD decreased after therapy in the atorvastatin group (13.22+/-3.39 & 11.85+/-2.87; 11.85+/-2.72 & 10.73+/-2.31; and 11.04+/-1.99 & 10.15+/-1.75, P < 0.05). There was no difference in the control group (13.29+/-2.89 & 13.93+/-2.89; 11.52+/-2.25 & 12.31+/-2.22; and 10.46+/-1.86 & 11.15+/-1.85, P > 0.05). After treatment, values of total cholesterol, triglyceride and low density lipoprotein (LDL) cholesterol were reduced in the 2 groups (P < 0.05). CONCLUSIONS: The study demonstrated that atorvastatin can improve arterial stiffness in CAD patients independent of its lipid-lowering properties.

Assessment of arterial stiffness, a translational medicine biomarker system for evaluation of vascular risk.

AIMS: Stiffening of the large arteries is a common feature of aging and is exacerbated by a number of disorders such as hypertension, diabetes, and renal disease. Arterial stiffening is recognized as an important and independent risk factor for cardiovascular events. This article will provide a comprehensive review of the recent advance on assessment of arterial stiffness as a translational medicine biomarker for cardiovascular risk. DISCUSSIONS: The key topics related to the mechanisms of arterial stiffness, the methodologies commonly used to measure arterial stiffness, and the potential therapeutic strategies are discussed. A number of factors are associated with arterial stiffness and may even contribute to it, including endothelial dysfunction, altered vascular smooth muscle cell (SMC) function, vascular inflammation, and genetic determinants, which overlap in a large degree with atherosclerosis. Arterial stiffness is represented by biomarkers that can be measured noninvasively in large populations. The most commonly used methodologies include pulse wave velocity (PWV), relating change in vessel diameter (or area) to distending pressure, arterial pulse waveform analysis, and ambulatory arterial stiffness index (AASI). The advantages and limitations of these key methodologies for monitoring arterial stiffness are reviewed in this article. In addition, the potential utility of arterial stiffness as a translational medicine surrogate biomarker for evaluation of new potentially vascular protective drugs is evaluated. CONCLUSIONS: Assessment of arterial stiffness is a sensitive and useful biomarker of cardiovascular risk because of its underlying pathophysiological mechanisms. PWV is an emerging biomarker useful for reflecting risk stratification of patients and for assessing pharmacodynamic effects and efficacy in clinical studies.

Assessment of ischemia-induced microvascular remodeling using contrast-enhanced ultrasound vascular anatomic mapping.

Our aim was to apply novel contrast-enhanced ultrasound (CEU) techniques to characterize remodeling in different vascular compartments during ischemia-mediated angiogenesis. Hind limb ischemia was produced by ligation of an external iliac artery in 60 rats, half of which were treated with intramuscular fibroblast growth factor (FGF)-2 (5 microg). The proximal adductor muscles of the ischemic and control hind limb were studied immediately after ligation and at days 4, 7, or 14. Low-power maximum intensity projection imaging was performed to assess large intramuscular vessels to the fourth branch order. CEU data were analyzed to measure capillary perfusion and functional noncapillary microvascular blood volume. Resting capillary perfusion was reduced by 30% after arterial ligation and recovered earlier in FGF-2-treated versus nontreated rats (day 4 vs. 14). Changes in perfusion were temporally related to expansion of noncapillary microvascular blood volume on CEU, which was associated with an arteriogenic response on histology. Expansion of and organization (fractal distribution) of large collateral vessels occurred gradually over 2 weeks and was slightly more rapid with FGF-2 treatment. We conclude that CEU can separately assess collateral development, more distal arteriogenesis, and secondary changes in capillary perfusion that occur differentially with ischemia and growth factor therapy.

Non-invasive assessment of arterial stiffness indices by applanation tonometry and pulse wave analysis in patients with rheumatoid arthritis treated with TNF-alpha blocker remicade (infliximab).

Rheumatoid arthritis (RA) is accompanied by long lasting inflammation, which may lead to arterial dysfunction and premature aging of the arteries. The purpose of this clinical work was to determine the modification of carotid-radial pulse wave velocity (PWV) and aortic augmentation index (AIx) in young-aged RA patients and the influence of treatment with anti-TNF-alpha (infliximab) on these measures. We examined 68 RA patients (mean age 40.68 yrs) with moderate or high disease activity (DAS28 5.37 +/- 0.94) and 87 controls (mean age 38.10 yrs). PWV and AIx were assessed non-invasively by applanation tonometry. A blood test included serum lipid profile, and high-sensitivity CRP measurements. We found that in RA patients, AIx (p < 0.001) was significantly higher while PWV (p = 0.315) did not differ as compared to control. Multiple regression analysis revealed the presence of RA is an independent predictor for AIx (R2 = 0.718, adjusted R2 = 0.707; p < 0.001). Analysis (Mann-Whitney test) in 15 RA patients revealed lowering of PWV (p = 0.004) under infliximab therapy with no change in AIx (p = 0.573), suggesting the improvement of arterial wall function by anti-TNF-alpha therapy. We conclude that increased AIx is more prominent in RA patients as compared to the controls. PWV appears to be a less sensitive marker for the detection of enhanced development of arterial stiffness in relatively young-aged RA patients. However, PWV may serve as a good marker to discern effects of infliximab on artery elasticity.

Indomethacin blocks the nucleus pulposus-induced effects on nerve root function. An experimental study in dogs with assessment of nerve conduction and blood flow following experimental disc herniation.

Inflammatory mechanisms have been suggested to be involved in the basic pathophysiologic events leading to nerve root injury after local application of nucleus pulposus. To assess if these nucleus pulposus-induced effects could be blocked by anti-inflammatory treatment, 41 dogs were exposed to either incision of the L6-7 disc to induce experimental disc herniation with (n=12) or without (n=14) indomethacin treatment per os (5 mg/kg per day), and no incision with (n=5) or without (n=10) indomethacin. Intraneural blood flow and nerve conduction velocity were assessed after 7 days to evaluate the degree of nerve injury. Disc incision induced a reduction in nerve root and dorsal ganglion blood flow as well as nerve function, similarly to previous studies. However, simultaneous treatment with indomethacin efficiently blocked the negative effects on both blood flow and nerve conduction but had no effects per se. The present study thus indicates that inflammatory mechanisms may be of relevance in the pathophysiology of nucleus pulposus-induced nerve root injury and thereby also for sciatica.

Noninvasive assessment of arterial stiffness and risk of atherosclerotic events.

Investigation of arterial stiffness, especially of the large arteries, has gathered pace in recent years with the development of readily available noninvasive assessment techniques. These include the measurement of pulse wave velocity, the use of ultrasound to relate the change in diameter or area of an artery to distending pressure, and analysis of arterial waveforms obtained by applanation tonometry. Here, we describe each of these techniques and their limitations and discuss how the measured parameters relate to established cardiovascular risk factors and clinical outcome. We also consider which techniques might be most appropriate for wider clinical application. Finally, the effects of current and future cardiovascular drugs on arterial stiffness are also discussed, as is the relationship between arterial elasticity and endothelial function.

Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension.

OBJECTIVE: Angiotensin Converting Enzyme Inhibitors (ACEIs) have been clearly proven to be effective in blood pressure control and haemodynamic control in heart failure patients. Moreover, there is evidence that ACEIs, both in animal models and in humans, also possess the ability to reduce remodeling in cardiovascular structures. Therefore, the reduction of the occurrence of arterial stiffness, leading to an increase in distensibility, is also anticipated. METHOD: Other than physically measuring arterial wall, the assessment of Pulse Wave Velocity (PWV) is also a widely used index of arterial distensibility, which deteriorates through the course of remodeling. To determine the efficacy of a particular ACEI, perindopril, in increasing arterial distensibility, thus reducing PWV, a 6-month multi-center study was conducted in 146 patients with mild to moderate hypertension. The study population consisted of 70 men and 76 women, aged 56.36 (SD 9.4, range 28-73) years. 73 patients were newly diagnosed, 65 were treated patients but the blood pressure was not controlled, and 8 were treated patients with their blood pressure controlled but with adverse effects in need of switching treatment regimens. RESULTS: Mean blood pressure at the beginning of the study was 164.25/97.49 mmHg and 11.71 m/s (SD 2.29 range 7.35-20.12 m/s) in mean PWV. Perindopril was prescribed tritrating from 4 mg/day to 8 mg/day and adding a diuretic. 106 patients completed the study with 76.4 per cent of patients having their blood pressure controlled (Mean Blood pressure 138.6/85.18 mmHg, SD 11.34 and 7.10 Range 110-170/70-110 mmHg) (p<0.05). Mean PWV reduced to 10.56 m/s (-9.89%) (SD 1.84 range 7.27-15.96 m/s) (p<0.05). CONCLUSION: Anti-hypertensive treatment with perindopril for 6 months was effective in controlling blood pressure and reducing Pulse Wave Velocity reflecting the increase of arterial distensibility.

Structural and functional assessment of small arteries in patients with chronic heart failure.

The physiological response to a chronically failing heart is the implementation of compensatory mechanisms intended to support blood pressure. These mechanisms, which are not fully understood, increase peripheral vascular tone, thus increasing the strain on the weakened myocardium. This study investigated the structure and function of small arteries from heart failure patients and controls without heart failure in an attempt to identify abnormalities associated with heart failure which may be related to these mechanisms. Small arteries were dissected from gluteal biopsies and studied using wire myography. Arterial morphological parameters were measured and concentration-response curves constructed for a number of vasoconstrictor and vasodilator agonists. Plasma concentrations of neuroendocrine hormones were also measured. There were no morphological differences between small arteries from control subjects and those from patients with chronic heart failure. In heart failure patients, vasoconstrictor responses to endothelin-1 were significantly reduced, although plasma endothelin-1 levels were increased. Arteries from heart failure patients also showed evidence of an impaired neuronal uptake mechanism, since blockade by cocaine had no effect on noradrenaline-induced vasoconstriction in these vessels. These results suggest that small-artery structure is not altered in chronic heart failure and so cannot account for the heightened vascular resistance in this syndrome. However, abnormal neuronal uptake and impaired vasoconstriction in response to endothelin-1 may be associated with the complex compensatory phenomenon involved in heart failure.

Assessment of the acute arterial effects of converting enzyme inhibition in essential hypertension: a double-blind, comparative and crossover study.

In subjects with essential hypertension, angiotensin-converting enzyme (ACE) inhibition increases arterial diameter, compliance and distensibility of peripheral muscular arteries in association with blood pressure reduction. Whether pulse pressure amplification is modified by ACE inhibition and whether changes in compliance and distensibility are due to a drug effect on the arterial wall, to the blood pressure reduction or to a combination of both factors, is largely ignored. In a randomised, double-blind crossover trial, we used the ACE inhibitor quinapril as a marker to evaluate the changes in: pulse pressure amplification (applanation tonometry), carotid compliance and distensibility (echo-tracking technique), and aortic distensibility (measured from pulse wave velocity). Quinapril decreased in the same extent carotid and brachial pulse pressure, thus causing a resetting of pulse pressure amplification toward normal values. Carotid compliance and distensibility as well as aortic distensibility increased significantly. Based on three-way analysis of variance, it was shown that, whereas the changes in carotid stiffness were exclusively due to blood pressure reduction and not to a drug-induced relaxation of the arterial wall, the changes in aortic distensibility were due to the combination of both factors. Thus, using an atraumatic non-invasive procedure, it was possible to show that: (i) ACE inhibition is able to maintain pulse pressure amplification, an important factor contributing to reduce the afterload of the heart; and (ii) ACE inhibition alters the hypertensive arterial wall in a very heterogeneous manner, with a maximal drug effect on muscular large arteries like the abdominal aorta, and not on elastic arteries like the carotid artery and the thoracic aorta.

Noninvasive assessment of regional arteriolar and arterial dilating properties of lisinopril in healthy volunteers.

The effects of single oral doses of lisinopril (5 and 20 mg) on systemic and regional hemodynamics were investigated noninvasively in a placebo-controlled, randomized, double-blind, cross-over study of 6 healthy male volunteers. Lisinopril induced a dose-dependent (significant after 20 mg) and long-lasting (< or = 8 h) decrease in mean arterial pressure (MAP, approximately 11% after 20 mg) that was related to a decrease in total peripheral resistance (TPR), because simultaneously heart rate (HR) and cardiac output (CO) were unchanged. Brachial artery flow (+42 and +47% after 5 and 20 mg, respectively) and diameter (+8 and +9%) increased significantly, whereas brachial vascular resistance (-31 and -38%) decreased significantly from 2 to 8 h after drug intake. Common carotid artery flow (+20 and +24%) also increased significantly, whereas corresponding resistance (-18 and -26%) decreased significantly during the same period. Finally, CO was significantly redistributed toward the brachial and, to a lesser extent, the carotid vascular beds after both doses of lisinopril. We conclude that in healthy subjects lisinopril, at non- or slightly hypotensive doses, dilates both arterioles and large arteries and that this vasodilation is not homogeneous, affecting preferentially the brachial rather than the carotid vascular bed.

Low frequency arterial wall movements for indirect blood pressure measurement in man. Validation of a method for non-invasive assessment of blood pressure under the influence of isoprenaline and angiotensin.

In order to measure blood pressure noninvasively, the second derivative of the low frequency wall movements of the brachial artery were registered with a piezo-electric pressure probe during deflation of a Riva-Rocci cuff along with the actual cuff pressure. Two characteristic phenomena of this signal have been suggested to reflect systolic and diastolic blood pressure. Appearance of a positive spike phenomenon (S) was suggested to indicate systolic blood pressure and disappearance of a negative preanacrotic notch (D) to indicate diastolic blood pressure. To prove the validity of these suggestions, these phenomena were assessed in 10 young healthy males during isoprenaline and angiotensin induced changes of blood pressure. Intraarterial (A. radialis) and auscultatory (A. brachialis) blood pressures were recorded simultaneously. Determination of systolic blood pressure with the S phenomenon agreed well with invasive and auscultatory results. Invasive diastolic values agreed well with the cuff pressure at the last signal before disappearance of the preanacrotic notch (D1). Data from auscultation agreed less well with the D1 phenomenon. With increasing doses of isoprenaline, the diastolic measurements (D1) tended to be lower than the invasive ones. However, this discrepancy was far discreeter than that seen with ordinary auscultatory blood pressure measurement. We therefore conclude that registrations of low frequency arterial wall movements yield distinct characteristic spike phenomena useful for measurement of blood pressure in good agreement with the invasive method. In addition, the method provides clearly documented records and should be useful in situations which rely on a valid indirect method.