Arterial stiffness is suggested to be a replacement method to measurements of brachial diameter following the release of an ischemic stimulus. We tested this hypothesis by comparing resting large [C1] and small [C2] arterial stiffness (as well as total peripheral resistance [TPR]) with brachial flow mediated dilation (FMD, indicator of endothelial function). Furthermore, the anatomical location that C2 represents is unclear. Could this reflect microcirculatory changes? We tested this hypothesis by comparing C2 with concurrent microcirculatory responses. 29 subjects (aged 18 to 30 years) were investigated. A tonometer recorded the radial blood pressure; pulse waveform analysis (PWA) was used to calculate C1, C2 and TPR. These parameters were correlated with forearm FMD responses. FMD was taken as the

BACKGROUND: The Brooksby-Donald approach uses two flow probes to measure the inflow and outflow from an organ or vascular bed; the difference in flow can be time-integrated to assess changes in venous capacitance. OBJECTIVES: To measure changes in subdiaphragmatic venous capacitance and arterial conductance in acutely instrumented rabbits, and to document the acute vascular responses to intravenous injections of pharmacological agents. METHODS: In artificially ventilated, fentanyl-anesthetized New Zealand female rabbits, ultrasonic flow probes were attached to the descending thoracic aorta and inferior vena cava to measure subdiaphragmatic inflow and outflow. Systemic arterial and venous pressures were measured. Conductance was calculated as aortic flow divided by the difference between systemic arterial and venous pressures. Changes in capacitance were assessed by integrating flow differences. Nitroglycerin (NG), isoproterenol hydrochloride, phenylephrine hydrochloride (PE) and vasopressin (VP) were administered intravenously in stepwise injections, and transient conductance and capacitance responses were determined. RESULTS: NG significantly increased conductance and capacitance, while isoproterenol hydrochloride had significant effects only on conductance. Both VP and PE significantly decreased conductance and capacitance. CONCLUSIONS: The modified Brooksby-Donald approach used in the present study was validated by the observed concordant increases in conductance and capacitance caused by NG, and decreases caused by VP and PE. This approach may be useful to characterize specific comparative conductance-capacitance properties of various vasoactive agents.

Polyphenols in grape and wine have been suggested to contribute to the cardiovascular health benefits of the Mediterranean lifestyle. The reported effects of grape products on blood pressure (BP) remain, however, equivocal. In a double-blind placebo controlled crossover study, the effect of two grape extracts on BP and vascular function was assessed in 60 untreated, mildly hypertensive subjects after four weeks intervention. Both extracts (grape-red wine and grape alone) had high concentrations of anthocyanins and flavonols, but the grape alone was relatively poor in catechins and procyanidins. Parameters measured included ambulatory and office BP, flow-mediated vasodilation, arterial distensibility, platelet function and plasma lipoproteins. Results showed that 24-hour ambulatory systolic/diastolic BPs were significantly lower in the grape-wine extract intervention (135.9 ± 1.3/84.7 ± 0.8 mmHg; mean ± SEM) compared to placebo (138.9 ± 1.3/86.6 ± 1.2 mmHg), predominantly during daytime. Plasma concentrations of the vasoconstrictor endothelin-1 decreased by 10%, but other measures of vascular function were not affected. Grape juice extract alone had no effect on BP or any measures of vascular function. Polyphenol-rich food products, and may be specifically catechins and procyanidins, may thus help sustain a healthy BP and contribute to the healthy Mediterranean lifestyle.

Some over-the-counter natural remedies claim to provide symptomatic relief from the common cold and flu. The current study used pubmed to review the evidence to support the use of garlic, onion, chilli and chocolate for the symptomatic relief of cold and flu symptoms, congestion, cough, mucous and a runny nose. The search terms focused the search on review articles conducted in humans. Results showed that there was limited data supporting the use of garlic, onion, chilli and chocolate. Future studies are required to support the effectiveness and safety of these ingredients alone or in combination. Studies may also consider exactly what ingredients are effective, which combinations are effective and at what dose these ingredients are effective.

Large (C1) and small (C2) arterial stiffness has been suggested to parallel endothelial reactivity and has led researchers to suggest parameters of arterial stiffness may be alternative measures to brachial sonographic assessments of flow-mediated dilatation (FMD). However, past studies comparing these measures can be criticized. In addition to %FMD responses, we recorded concurrent hyperaemic responses of the microcirculation and both were compared with C1 and C2. Twenty-nine subjects 18-30 years of age were investigated. Radial blood pressure was recorded with a tonometer. Pulse waveform analysis was performed to calculate C1 and C2. These were compared with %FMD responses and responses of finger flux measured by laser Doppler fluxmetry (LDF); pulsatile finger volume measured by photoplethysmography (PPG); and palm skin temperature measured by infrared thermography (T(palm)) (i.e. microcirculatory responses). Responses were determined as % changes from control. We only found weak relationships between C1 and %FMD (r = 0.4, P = 0.04); C2 and %PPG (r = 0.38, P = 0.07); and C2 and %LDF(dorsal) (r = -0.38; P = 0.04). Responses of %FMD weakly parallel those of C1. Neither C2 nor C1 are viable indicators of endothelial or microcirculatory reactivity (i.e. hyperaemic or venous constriction) in healthy, resting young males. These findings refute the claims that C1 and C2 are substitute measures to sonographic assessments of brachial FMD.

BACKGROUND: Transient bradycardic hypotensive events occur in resting rabbits. If the hypotension is due to vasodepression, these events may be a model for vasovagal syncope.OBJECTIVES: To determine whether these events are responses to brief Stimuli and whether the hypotensive episodes are solely due to rapid-onset bradycardia.METHODS: Rabbits were instrumented with subcutaneous electrocardiogram leads, and cannulae were acutely inserted into an ear artery to obtain continuous arterial pressure measurements. Exposure to brief, low-level auditory Stimuli at 5 kHz transiently increased the RR interval by approximately 70 ms and decreased mean arterial pressure by approximately 5 mmHg.RESULTS: These evoked bradycardic hypotensive events were almost identical to previously reported spontaneous bradycardic hypotensive events. Intra-aortic telemetric blood pressure monitoring was used to demonstrate that the evoked hypotension reflected prolonged diastole, rather than local ear arterial vasoconstriction. Furthermore, administration of the muscarinic blocker glycopyrrolate abolished not only bradycardia (RR interval 64 +/- 14 ins to 1 +/- 1 ms; P < 0.0001), but also hypotension (-4.1 +/- 0.8 mmHg to -0.4 +/- 0.3 mmHg; P=0.0055). Finally, cardiac pacing abolished the inducible bradycardia (RR interval 51 +/- 10 ins to 2 +/- 1 ins; P=0.0006) and its associated hypotension (-4.1 +/- 0.7 mmHg to -1.2 +/- 0.3 mmHg; P=0.003).CONCLUSIONS: Brief auditory stimuli evoked a transient bradycardia mediated by cardiac muscarinic receptors and consequent hypotension. This is not a model for vasovagal syncope.

Local wall stiffness affects endothelial responsiveness but how global measures affect responsiveness is unanswered. We assessed this by comparing reactive hyperaemic responses of brachial diameter (RHRBD) with central (heart-to-brachial artery pulse wave velocity (PWV); large (C1)) and peripheral (C2) arterial stiffness. Twelve healthy subjects were investigated. RHRBD was induced via an upper-or forearm occluding cuff. Arterial diameter changes were measured using echo ultrasound. Arterial stiffness and RHRBD were compared using a Pearson correlation coefficient (r) and Bland - Altman analysis of Z-scores (indicated as 95% confidence intervals (CI) and expressed in units of standard deviation (SD) from the mean). Weak relations were found between upper-arm RHRBD responses and C2 (r = 0.56, P = 0.06; 95% CI +/- 1.84 SDs) and C1 (r = 0.55, P = 0.06; 95% CI +/- 1.86 SDs). An inverse relation was found between upper- arm RHRBD responses and PWV ( r=-0.55, P=0.06), but Bland - Altman plots revealed no agreement between these parameters ( P > 0.05; 95% CI +/- 3.46 SDs). Forearm RHRBD were not related to PWV, C1 or C2 ( P > 0.05; 95% CI > 2 SDs). The weak relation between upper-arm endothelial responses and C2 and C1 seems to suggest that C2, and also C1, is not a good and reliable method for assessments of endothelial health. Furthermore, if anything, upper-arm mediated RHRBD responses are more affected by arterial stiffness than forearm responses.

BACKGROUND/OBJECTIVES:Vitamins can help improve cardiovascular control. In contrast, smoking works in the opposite fashion, reducing the baroreflex control of heart rate (HR) possibly via oxidative stress. High-fat challenges also impair cardiovascular regulation. Whether vitamins have acute beneficial effects on the baroreflex control of HR in smokers is unclear. SUBJECTS/METHODS:A randomized, placebo-controlled crossover study in 30 male smokers (34.2+/-6.9 years). Interventions were: (1) moderate (vitamin C (300 mg) and E (75 IU) and folic acid (1 mg)); (2) high doses of vitamins (vitamin C (2 g) and E (800 IU), and folic acid (5 mg)); or, (3) placebo. Vitamins were ingested with cream (a high-fat challenge) or milk (low-fat control). Four hours later, blood was withdrawn and radial pulse wave forms recorded via tonometry. Spontaneous beat-to-beat variations in HR and systolic blood pressure (SBP) were analysed by spectral analysis techniques and sympathovagal control of HR and baroreflex sensitivity (BRS) were assessed. RESULTS:High doses of vitamins increased plasma vitamin C, E and folic acid levels (P<0.05) with no change in SBP, HR or BRS (P>0.05, analysis of variance). Plasma vitamin levels did not correlate with any cardiovascular parameters. Moderate vitamins increased the vagal control of HR (+23%; P<0.05) and cream led to small increases (P<0.05) in SBP (+2 mm Hg) and HR (+2 beats min(-1)) with no change in BRS. CONCLUSIONS:In male smokers, circulating antioxidants had no effect on BRS and minor effects on the cardiovascular system were seen following acute fat and vitamin ingestion.

There is increasing interest in the health and wellness benefits of herbs and botanicals. This is with good reason as they might offer a natural safeguard against the development of certain conditions and be a putative treatment for some diseases. One such area may be the lowering of blood pressure in those where it is elevated (i.e., hypertension). One class of clinical medicines used to lower blood pressure are known as diuretics and work by increasing the excretion of urine from the body as well as the amount of sodium in urine. There are a growing number of studies purporting diuretic effects with traditional medicines. The aim of this article was to review these studies and identify which extracts promote diuresis (which we assessed on terms of urine excreted and urinary sodium excretion) and also to identify the research needs in this area. We identified a number of species and genuses reporting diuretic effects. Of these, the most promising, at the present time, are the species Foeniculum vulgare, Fraxinus excelsior, Hibiscus sabdariffa, Petroselinum sativum and Spergularia purpurea, and species from the genuses Cucumis (Cucumis melo and Cucumis trigonus), Equisetum (Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum), Lepidium (Lepidium latifolium and Lepidium sativum), Phyllanthus (Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus) and Sambucus (Sambucus mexicana and Sambucus nigra). However, there the number of studies is limited and we recommend that further studies be conducted to confirm reported effects. Such evidence is needed to provide scientific credence to the folklore use of traditional medicines and even be helpful in the development of future medicines, treatments and treatment guidelines.

Vessels in the skin are arranged into superficial and deep horizontal plexuses and they are involved in thermoregulation, oxygen and nutritional support. The skin has a large number of functions and broad appeal spanning basic mechanistic and clinical research. Indeed, the skin can be used as a marker of normal and impaired vascular control and, owing to its accessibility and frequent involvement, is easy to investigate non-invasively. A large number of non-invasive methods are available for investigating the skin, ranging from those that permit the visualisation of microvessels, to those that monitor blood flow or one of its derivatives (e.g., skin temperature and transcutaneous oxygen). Such methods can be combined with non-invasive, dynamic stimuli (e.g., the use of cold or warm stimuli, activation of the peripheral nervous system or local neuronal systems, and the topical application of vasoactive drugs) and this potentially enables the differentiation of underlying disorders (e.g., primary from secondary Raynaud's phenomenon) and also to quantify changes over time or following intervention. The present article outlines the non-invasive methods and dynamic tests that can be used to investigate the microcirculation of the skin.

In this article we focus on the possible use of foods to alleviate Raynaud's phenomenon (RP). RP is evoked, predominately, by cold and results in a potent vascular constriction of the microvascular blood vessels in the hands, thus leading to reduced hand blood flow and the elevation of pain sensation. To alleviate RP by diet, food components need to be able to promote hand skin blood flow, which may be achieved using fish oil, garlic, ginkgo biloba, L-carnitine, or inositol nicotinate, or to increase hand skin temperature, using evening primrose oil, ginkgo biloba, or inositol nicotinate. Although there are a number of studies documenting such improvements with these ingredients, they often are poorly designed. Hence, there is a need for more controlled studies to substantiate their use, but also to test alternative foods or target new ones. Therefore, we also discuss some alternate food options and briefly outline clinical drugs for the treatment of RP, as their mechanisms of action may also be possible targets for food. It is the intention of this article to address the research needs of this field and to provide a better understanding of alternative options for those with RP.

BACKGROUND:The Brooksby-Donald approach uses two flow probes to measure the inflow and outflow from an organ or vascular bed; the difference in flow can be time-integrated to assess changes in venous capacitance.OBJECTIVES:To measure changes in subdiaphragmatic venous capacitance and arterial conductance in acutely instrumented rabbits, and to document the acute vascular responses to intravenous injections of pharmacological agents.METHODS:In artificially ventilated, fentanyl-anesthetized New Zealand female rabbits, ultrasonic flow probes were attached to the descending thoracic aorta and inferior vena cava to measure subdiaphragmatic inflow and outflow. Systemic arterial and venous pressures were measured. Conductance was calculated as aortic flow divided by the difference between systemic arterial and venous pressures. Changes in capacitance were assessed by integrating flow differences. Nitroglycerin (NG), isoproterenol hydrochloride, phenylephrine hydrochloride (PE) and vasopressin (VP) were administered intravenously in stepwise injections, and transient conductance and capacitance responses were determined.RESULTS:NG significantly increased conductance and capacitance, while isoproterenol hydrochloride had significant effects only on conductance. Both VP and PE significantly decreased conductance and capacitance.CONCLUSIONS:The modified Brooksby-Donald approach used in the present study was validated by the observed concordant increases in conductance and capacitance caused by NG, and decreases caused by VP and PE. This approach may be useful to characterize specific comparative conductance-capacitance properties of various vasoactive agents.

BACKGROUND: Changes in intestinal vascular capacitance during acute volume loading and hemorrhage have not been described.OBJECTIVES: To determine the effects of volume loading and hemorrhage on the intestinal vascular pressure-volume relationship and cardiac output.PATIENTS AND METHODS: In 11 alpha-chloralose-anesthetized dogs, a pneumatic portal venous constrictor and catheter were positioned to increase and measure portal venous pressure (P-pv), respectively. Relative changes in intestinal blood volume (IBV) were deter-mined by blood-pool scintigraphy and expressed as the percentage change from control values (taken as 100%). P-pv-IBV relationship, were constructed by graded portal vein constriction.RESULTS: IBV and cardiac Output increased by 60 +/- 6% and 178 +/- 48%, respectively, and P-pv increased from 5.8 +/- 0.9 mmHg to 13.2 +/- 1.8 mmHg after initial volume loading (40 mL/kg of an isotonic glucose-saline solution over 7 min). IBV gradually decreased and reached near-control values after 75 min. In seven dogs, hemorrhage (sufficient to decrease mean aortic pressure by 56 +/- 4%) decreased IBV and cardiac output to 88 +/- 4% and 52 +/- 3% of control values, respectively, and P-pv decreased to 3.2 +/- 0.8 mmHg.CONCLUSIONS: A sigmoid function curve defined the relationship between cardiac output and IBV. Cardiac output remained constant over a wide range (between approximately I is 95% and 135% of control IBV). Outside this range, insufficient dilation or constriction resulted in a marked increase or decrease in venous pressures and cardiac output. These data indicate that vasculature capacitance modulates cardiac output during acute volume loading and hemorrhage, thereby maintaining cardiac output relatively constant over a wide range of total vascular blood volume.

Stimulation of left ventricular mechanoreceptors was believed not only to exert important effects on the circulation, but also to influence the responses to baroreceptor reflexes. However, most previous work is flawed due to inadequate localisation of stimuli to specific reflexogenic areas. In this study, we applied a discrete stimulus to left ventricular mechanoreceptors to examine other reflexes known to effect the circulation. Dogs were anaesthetised, artificially ventilated and a cardiopulmonary bypass established. The pressure distending the left ventricle was controlled through an apical cannula with the aortic valve obstructed by a balloon. Changes in ventricular systolic and end‐diastolic pressure had only a small effect on vascular resistance, assessed as perfusion pressure in the systemic circulation (flow constant). Responses to changes in carotid or coronary pressure or to stimulation of chemosensitive afferents by injecting veratridine into the coronary circulation were always much larger. Responses to stimulation of these reflexes were little affected by the level of stimulus to the ventricular receptors. These experiments confirm that responses to stimulation of ventricular mechanoreceptors are very small and show that they remain small at different levels of input to other baroreceptive regions. There was no evidence of interaction between ventricular mechanoreceptor reflexes and carotid or coronary baroreceptors or ventricular chemosensitive reflexes.

1. Ventricular mechanoreceptors are known to exist and can when stimulated induce reflex vasodilatation, but the nature of the effective stimuli and the physiological role of the reflex remain to be established.2. Dogs were anaesthetised with chloralose and a cardiopulmonary bypass established. Ventricular pressures were separated from those in the aortic root and coronary arteries by a balloon inflated in the ventricular outflow tract. Ventricular filling was controlled by adjusting the rate of inflow of blood through an apical cannula and peak pressure by regulating the outflow pressure from the same cannula. Carotid and aortic pressures were also controlled and vascular resistance was assessed from changes in perfusion pressure (constant flow conditions) to the descending abdominal aorta.3. Increased coronary or carotid sinus pressure induced a significant vasodilatation. Changes in ventricular peak systolic pressure, without associated changes in end-diastolic pressure, had no significant effect on vascular resistance. In contrast, changes in end-diastolic pressure did induce vasodilatation that, although small, was proportional to the magnitude of the end-diastolic pressure change.4. Changes in ventricular inotropic state induced by dobutamine infusion or by stimulation of efferent cardiac sympathetic nerves did not induce significant responses. Furthermore, the combined effects of reduced ventricular filling and increased inotropic state were also ineffective in inducing responses.5. We conclude that, to induce reflex responses, the only effective stimulus to ventricular mechanoreceptors was an increase in filling. Compared with other mechanoreflexes, however, responses to ventricular distension were small and seem unlikely to be of importance except perhaps during abnormal ventricular distension.

1 Previous studies which have indicated that the stimulation of ventricular mechanoreceptors induces significant reflex responses can be criticised because of the likelihood of concomitant stimulation of coronary arterial baroreceptors. We therefore undertook this investigation to examine the coronary and ventricular mechanoreflexes in a preparation in which the pressure stimuli to each region were effectively separated. 2 Dogs were anaesthetised, artificially ventilated and placed on cardiopulmonary bypass. A balloon at the ventricular outflow separated pressure in the left ventricle from that perfusing the coronary arteries. Ventricular pressures were changed by varying inflow and outflow of blood entering and leaving the ventricle through an apical cannula, and coronary pressure by changing pressure in a reservoir connected to a cannula tied in the aortic root. Pressures distending carotid and aortic baroreceptors were controlled. Changes in descending aortic perfusion pressure (flow constant) were used to assess systemic vascular responses. 3 Large changes in carotid sinus and coronary pressures decreased vascular resistance by 35 ± 1.9 and 40 ± 2.5 %, respectively. Intracoronary injections of veratridine (30–60 μg) decreased vascular resistance by 31 ± 2.5 %. However, large increases in ventricular pressure decreased resistance by only 9 ± 2.2 %. 4 Significant changes in vascular resistance were obtained with increases in coronary arterial pressure from 60 to 90 mmHg. However, ventricular pressures had to increase to 152/18 mmHg (systolic/end‐diastolic) before there was a significant response. 5 These results show that coronary mechanoreceptors are likely to play an important role in cardiovascular control. If ventricular receptors have any function at all, it is as a protective mechanism during gross distension, possibly associated with myocardial ischaemia.