Chloroethylclonidine and alpha-adrenoceptor agonist interaction in blood vessels following heart failure

We compare and contrast the putative mechanisms underlying CO2 chemoreceptor function in air breathing vertebrates and terrestrial pulmonate snails. We discuss the role of intracellular pH (pHi) in central respiratory responses to CO2 and describe a variety of patterns of pHi regulation in chemosensory areas. One pattern, in which pHi retains a fixed relationship to the CO2 stimulus over time, seems well suited to chemoreceptor cells. Alphastat regulation of ventilation is apparent in both air breathing vertebrates and terrestrial pulmonate snails. Diethyl pyrocarbonate inhibits respiratory responses to hypercapnia in both groups of animals. The neuronal basis of chemosensitivity is similar, in that putative chemoreceptor cells depolarize during hypercapnic stimulation, but the ionic basis of excitability appears to be a potassium conductance in the vertebrates studied to date and a calcium conductance in the snails. Despite divergent evolutionary histories, chemosensory responses and mechanisms are remarkably similar in air breathing vertebrates and terrestrial pulmonate snails.     

Changes in sympathetic activity to heart and blood vessels during desynchronized sleep

In mid-collicular decerebrate cats, the activity in sympathetic nerves to the heart, kidney, gastro-intestinal tract, pelvic viscera and blood vessels of skeletal muscle was examined during periods of extensor rigidity and during desynchronized sleep-like periods (DSp) either occurring spontaneously or induced by physostigmine sulphate. During DSp the activity in sympathetic vasoconstricstor fibres to muscle increased whereas that in the other sympathetic nerves decreased. The changes were present in vagotomized and sino-aortic denervated animals as well as in paralyzed preparations. It was concluded that the differential pattern of sympathetic activity was a characteristic of the tonic stage of desynchronized sleep and originated from a site in the central nervous system independently of afferent input.     

Leptin and the regulation of body weight in mammals

The assimilation, storage and use of energy from nutrients constitute a homeostatic system that is essential for life. In vertebrates, the ability to store sufficient quantities of energy-dense triglyceride in adipose tissue allows survival during the frequent periods of food deprivation encountered during evolution. However, the presence of excess adipose tissue can be maladaptive. A complex physiological system has evolved to regulate fuel stores and energy balance at an optimum level. Leptin, a hormone secreted by adipose tissue, and its receptor are integral components of this system. Leptin also signals nutritional status to several other physiological systems and modulates their function. Here we review the role of leptin in the control of body weight and its relevance to the pathogenesis of obesity.     

Central neural correlates of learned heart rate control during exercise: central command demystified

To identify the brain areas involved in central command, four monkeys were trained to attenuate the tachycardia of exercise while different brain sites affecting heart rate (HR) were simultaneously stimulated electrically. Among 24 brain sites located mostly in the limbic structures, we have identified four types of control systems that mediate cardiovascular and motor behavior during exercise. One system increases HR equivalently during both exercise and operantly controlled HR, whereas another increases HR during both tasks and abolishes operant HR control. In the third system, the effect of brain stimulation on HR is attenuated during exercise and during exercise with operantly controlled HR. The fourth system increases HR in both tasks, but its effect is significantly attenuated during operant HR control. We believe that this last system, which includes the mediodorsal nucleus, nucleus ventralis anterior, and cingulate cortex, plays a significant role in central command.     

Endothelium-smooth muscle interactions in blood vessels

1. Blood vessel tone is determined both by smooth muscle and endothelial functions. In coronary arteries taken from rat (Fisher-Lewis) cardiac transplanted hearts, the inducible form of NOS (iNOS) in smooth muscle is more active, while acetylcholine-induced nitric oxide production in the endothelium is greatly diminished. This causes a greatly reduced myogenic constriction, in pressurized septal arteries taken from immunologically challenged transplanted hearts. 2. The sarcoplasmic reticulum (SR) of smooth muscle and the endoplasmic reticulum (ER) of endothelial cells sequester Ca2+ from the cytoplasm. This reduces the intracellular concentration of free Ca2+, which is necessary for the activation of cellular processes. The release of Ca2+ from internal stores occurs through ryanodine and IP3 recoptors located on the SR membrane. 3. The superficial SR/ER also interacts with ion exchangers and pumps in the plasma membrane. This allows for the superficial SR/ER to function in Ca2+ extrusion; for example, inhibition of the SR/ER Ca(2+)-ATPase (SERCA) partially inhibits the rate of loss Ca2+ from the cell. Recent data suggest that the SR Ca(2+)-ATPase and the Na(+)-Ca2+ exchanger of smooth muscle cells function in series; that is, Ca2+ uptake by the SR followed by release towards the exchanger to mediate extrusion. This interaction between the SERCA of the superficial SR and ion exchangers and pumps creates intracellular Ca2+ gradients. 4. The SERCA of the superficial, peripherally distributed SR/ER also serves to regulate Ca2+ entry from the extracellular space. This occurs in part by inhibition of the superficial buffer barrier function of the SR as well as by depletion of stimulated Ca2+ entry. 5. Ca2+ entry is also regulated in endothelial and smooth muscle cells by the membrane potential. Membrane hyperpolarization increases the driving force for Ca2+ entry into endothelial cells, which lack voltage-gated Ca2+ channels, and reduces open state probability of voltage-gated Ca2+ channels in vascular smooth muscle cells. The two cell types have electrical contact and interact in a dynamic manner to regulate blood vessel diameter.     

Clinical importance of intramural blood vessels in the sino-atrial segment of the conducting system of the heart

The perinatal implications of oligohydramnios prior to 37 weeks of gestation, in the absence of intrauterine growth restriction (IUGR), rupture of membranes or fetal anomalies, are unknown. We compared the outcomes of 65 women with oligohydramnios (amniotic fluid index ([AFI] < or = 8 cm) by sonography to those of a control group matched by sonogram indication. Study patients were between 17 and 37 weeks of gestation, with appropriately grown fetuses on index sonogram and no other detected explanation for amniotic fluid abnormalities. Patients were managed expectantly with fetal testing and follow-up sonograms for fetal growth. Delivery was not recommended solely for oligohydramnios until 37 weeks of gestation. Patients with isolated oligohydramnios prior to 37 weeks of gestation, when compared to a control group with normal amniotic fluid volume, had a significantly higher incidence of premature delivery (odds ratio [OR] 3.23, 95% confidence interval [CI] 1.4-7.3) but did not appear to be at increased risk of IUGR, intrauterine death, or birth asphyxia.     

Chronic 17beta-estradiol augments relaxant role of basal nitric oxide in blood vessels from rats with heart failure

It is estimated that approximately 27% of women have a history of childhood sexual abuse. Long-term effects of this abuse include physical and psychologic consequences that can affect the pregnant woman during the prenatal, antenatal, and postpartum periods. Careful screening of all pregnant women and specific interventions during examinations and procedures can help survivors of childhood sexual abuse experience childbearing as healing and empowering. Care providers who are survivors of such abuse can better serve their patients by working therapeutically on their own healing.     

Effects of chronic administration of alcohol on neural mechanisms of arterial blood pressure regulation]

Metaphor comprehension was studied in schizophrenics as compared to psychiatric and nonpsychiatric controls. Subjects were asked in a two-condition forced-choice response task to detect the metaphor similar or contrary to a proverb with an abstract meaning. Schizophrenic patients were impaired in both conditions. However, the paranoid patients' performances did not differ from psychiatric and nonpsychiatric controls. These results are consistent with the hypothesis that the ability of metaphorizing is preserved in some schizophrenic patients.     

Autonomic regulation of nasal vessels during changes in body position

The effects of postural changes on nasal airflow and nasal capillary blood flow were investigated in 15 healthy volunteers. Measurements were performed following nasal application of saline solution (control), the alpha-1 receptor antagonist prazosin, the alpha-2 receptor antagonist yohimbine, and after application of both prazosin and yohimbine. Nasal airflow in the control experiments did not significantly differ in the upright (362 +/- 166 ml/s), dorsally recumbent (350 +/- 167 ml/s) and 70 degrees head down position (311 +/- 167 ml/s). Following application of prazosin, nasal airflow was reduced to 223 +/- 121 ml/s in the upright position. Prazosin treatment significantly reduced nasal airflow to 177 +/- 111 ml/s when subjects were placed in dorsally recumbent positions and to 117 +/- 104 ml/s in 70 degrees head down positions (P < 0.001). Following application of yohimbine, nasal airflow remained stable when subjects were turned from upright (348 +/- 165 ml/s) to supine position (352 +/- 186 ml/s), whereas it was reduced to 199 +/- 137 ml/s in the head-down position. Application of both prazosin and yohimbine significantly increased nasal capillary blood flow in laser Doppler flowmetry measurements (P < 0.05). Changes in body position with or without application of the active drugs did not alter nasal capillary blood flow. These findings suggest that nasal congestion due to increased filling pressure in nasal capacitance vessels following postural changes is mainly prevented by alpha-1 adrenergic mechanisms.     

Overproduction of nitric oxide in pathophysiology of blood vessels

Sustained production of large amounts of nitric oxide (NO) is induced in blood vessels by inflammatory stimuli as a result of the expression of the inducible form of NO-synthase (NOS-2). This happens in systemic inflammatory reactions like septic shock and in local reactions produced by endothelium denudation and atherosclerosis. NOS-2 activity in blood vessels may protect tissues by virtue of the vasodilating, anti-thrombotic and leukocyte adhesion inhibitory effects of NO. It may also participate in vascular remodeling as a result of the antiproliferative and pro-apoptotic actions of NO. However excessive production of NO in blood vessels is involved in circulatory failure that takes place in systemic inflammatory reactions and it may be cytotoxic for surrounding tissues. For these reasons, inhibition of NO overproduction has been proposed in the treatment of septic shock. Selective inhibitors of NOS-2 activity or NO trapping agent, or both, might prove to be valuable drugs in the treatment of some inflammatory diseases. The conditions in which NO shifts from a tissue protective to a damaging role are not well elucidated. Recent findings suggest that the interactions with superoxide radicals, thiols, and metals (particularly with Fe2+) may be important not only in buffering excess NO produced by NOS-2, but also in channeling it from physiologically to pathophysiologically relevant targets. It has also been found recently that adventitial cells may play an important part in vascular NO production and generation of NO stores in the media layer. The ultimate effect of NO in blood vessels might depend on its site of production, local concentration, and interactions with other tissue components.