Cardiovascular reflex responses induced by epicardial chemoreceptor stimulation.
The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptors by topical application of chemical compounds elicits a variety of reflex cardiovascular responses, without the vascular or systemic effects of the drug administered systemically. A considerable number of studies has used the epicardial sensory field as a tool to delineate the functional characteristics of the cardiac afferent neurones in normal as well as in pathological conditions. In this review we analyze the cardiovascular reflex responses induced by epicardial application of a variety of substances like bradykinin, nicotine, muscarine, isoprenaline, adenosine, potassium chloride, capsaicin, prostaglandins or substance P in physiological models and also in models with acute myocardial ischemia or heart failure. The data highlight the contribution of the epicardial sensory neurites to the overall control of the cardiovascular system and, on the other hand, strengthen the need for further investigations directed to better elucidate the reflex cardiovascular responses that may develop in patients with pericardial abnormalities. (+info)
Signalling via stress-activated mitogen-activated protein kinases in the cardiovascular system.
A number of physiological, pharmacological and pathological stimuli initiate cardiac hypertrophy. The intracellular signalling events activated by these stimuli are equally complex. Our ability to treat the hypertrophic and failing myocardium effectively will require clarification of which signalling events regulate growth, remodelling and failure. Much recent attention has focused on the regulation of the mitogen-activated protein kinase cascades (MAPKs), with the importance of these cascades in the development of cardiovascular diseases being extensively explored. These signalling pathways may provide one link from the diverse stress and pharmacological extracellular stimuli to the regulation of gene expression, contractile protein regulation and protein function. This review focuses on the recent progress made in the understanding of the regulation and function of MAPKs in the cardiovascular system, with particular emphasis being placed on the events in the cardiac ventricular myocyte. (+info)
Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on D-methamphetamine-induced cognitive and physiological changes in humans.
D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans. (+info)
Influence of upper- and lower-limb exercise training on cardiovascular function and walking distances in patients with intermittent claudication.
PURPOSE: The effects of upper-limb (arm cranking) and lower-limb (leg cranking) exercise training on walking distances in patients with intermittent claudication was assessed. METHODS: Sixty-seven patients (33 to 82 years old) with moderate to severe intermittent claudication were recruited, and the maximum power generated during incremental upper- and lower-limb ergometry tests was determined, as were pain-free and maximum walking distances (by using a shuttle walk test). Patients were randomly assigned to an upper-limb training group (n = 26) or a lower-limb training group (n = 26). An additional untrained group (n = 15) was recruited on an ad hoc basis in parallel with the main trial by using identical inclusion criteria. This group was subsequently shown to possess a similar demographic distribution to the two exercise groups. Supervised training sessions were held twice weekly for 6 weeks. RESULTS: Both training programs significantly improved the maximum power generated during the incremental upper- and lower-limb ergometry tests (P <. 001), which may reflect an increase in central cardiovascular function that was independent of the training mode. More importantly, pain-free and maximum walking distances also improved in both training groups (P <.001). The improvements in the training groups were similar; there were no changes in the untrained control group. These findings suggest that the symptomatic improvement after upper-limb exercise training may result, in part, from systemic cardiovascular effects rather than localized metabolic or hemodynamic changes. CONCLUSION: Carefully prescribed upper-limb exercise training can evoke a rapid symptomatic improvement in patients with claudication, while avoiding the physical discomfort experienced when performing lower-limb weight-bearing exercise. (+info)
Functional analysis of cardiovascular renin-angiotensin system using a gain or loss of function approach.
The study of the effect of autocrine-paracrine vasoactive modulators on cardiovascular biology is very difficult in vivo, because in vivo studies are limited. In particular, characterization of the role of components of the renin-angiotensin system (RAS) in vivo is limited by the difficulty in manipulating individual components of the RAS as well as by methodological limitations in studying the function of a local RAS in the absence of any contribution by the circulatory system. Recent progress in in vivo gene transfer technologies has provided us with the opportunity to study cellular responses to the manipulation of the individual components (i.e., by overexpression or inhibition). Many researchers have recently developed various in vivo gene transfer techniques for cardiovascular applications. Using in vivo gene transfer approaches, the roles of various tissues in the RAS, such as cardiac angiotensin, have been identified. Such an approach may increase our understanding of the biology and pathobiology of the autocrine-paracrine system. This review discusses the potential utility of in vivo gene transfer methods. (+info)
The physiological role of AT1 receptors in the ventrolateral medulla.
Neurons in the rostral and caudal parts of the ventrolateral medulla (VLM) play a pivotal role in the regulation of sympathetic vasomotor activity and blood pressure. Studies in several species, including humans, have shown that these regions contain a high density of AT1 receptors specifically associated with neurons that regulate the sympathetic vasomotor outflow, or the secretion of vasopressin from the hypothalamus. It is well established that specific activation of AT1 receptors by application of exogenous angiotensin II in the rostral and caudal VLM excites sympathoexcitatory and sympathoinhibitory neurons, respectively, but the physiological role of these receptors in the normal synaptic regulation of VLM neurons is not known. In this paper we review studies which have defined the effects of specific activation or blockade of these receptors on cardiovascular function, and discuss what these findings tell us with regard to the physiological role of AT1 receptors in the VLM in the tonic and phasic regulation of sympathetic vasomotor activity and blood pressure. (+info)
NTS A(2a) purinoceptor activation elicits hindlimb vasodilation primarily via a beta-adrenergic mechanism.
Previously, we have shown that activation of adenosine A(2a) receptors in the subpostremal nucleus tractus solitarii (NTS) via microinjection of the selective A(2a) receptor agonist CGS-21680 elicits potent, dose-dependent decreases in mean arterial pressure and preferential, marked hindlimb vasodilation. Although A(2a) receptor activation does not change lumbar sympathetic nerve activity, it does markedly enhance the preganglionic adrenal sympathetic nerve activity, which will increase epinephrine release and could subsequently elicit hindlimb vasodilation via activation of beta(2)-adrenergic receptors. Therefore we investigated whether this hindlimb vasodilation was due to neural or humoral mechanisms. In chloralose-urethan-anesthetized male Sprague-Dawley rats, we monitored cardiovascular responses to stimulation of NTS adenosine A(2a) receptors (CGS-21680, 20 pmol/50 nl) in the intact control animals; after pretreatment with propranolol (2 mg/kg iv), a beta-adrenergic antagonist; after bilateral lumbar sympathectomy; after bilateral adrenalectomy; and after combined bilateral lumbar sympathectomy and adrenalectomy. After beta-adrenergic blockade, stimulation of NTS adenosine A(2a) receptors produced a pressor response and a hindlimb vasoconstriction. Lumbar sympathectomy reduced the vasodilation seen in the intact animals by approximately 40%, and adrenalectomy reduced it by approximately 80%. The combined sympathectomy and adrenalectomy virtually abolished the hindlimb vasodilation evoked by NTS A(2a) receptor activation. We conclude that the preferential, marked hindlimb vasodilation produced by stimulation of NTS adenosine A(2a) receptors is mediated by both the efferent sympathetic nerves directed to the hindlimb and the adrenal glands via primarily a beta-adrenergic mechanism. (+info)
Reducing stress responses in the pre-bypass phase of open heart surgery in infants and young children: a comparison of different fentanyl doses.
High-dose opioids are advocated for paediatric cardiac surgery to suppress stress responses but they can produce unwanted side effects. There are no data on the dose-dependent effects of opioids on the stress response on which to base rational opioid administration. We conducted a dose ranging study on 40 children less than 4 yr undergoing elective open heart surgery using one of five fentanyl doses: 2, 25, 50, 100 or 150 micrograms kg-1 before surgery. The standardized anaesthetic also included pancuronium and isoflurane. Blood samples were taken at induction, before incision, after sternotomy, immediately before, and at the end of cardiopulmonary bypass. Patients in the 2 micrograms kg-1 group had significant rises in prebypass glucose (P < 0.01), pre- and post-bypass cortisol (P < 0.01), and pre- and post-bypass norepinephrine (P < 0.01). No significant rise occurred in glucose, cortisol and catecholamines in any of the higher dosage groups. Patients in the 2 micrograms kg-1 group had significantly higher mean systolic blood pressure (P < 0.02) and heart rate (P < 0.04). A balanced anaesthetic containing fentanyl 25-50 micrograms kg-1 is sufficient to obtund haemodynamic and stress responses to the pre-bypass phase of surgery. Higher doses of fentanyl (100 and 150 micrograms kg-1) offer little advantage over 50 micrograms kg-1, and can necessitate intervention to prevent hypotension. (+info)