Adrenergic responses

It has been proposed that NO mediates the myocardial depression associated with sepsis (F6, L14). NO synthesis induced by endotoxin blunts beta-adrenergic responsiveness (B2). In vivo, the use of NO synthase inhibitors led to conflicting results (M26), with a general decreased cardiac output and oxygen delivery being observed. NO synthase inhibition improved left ventricular contractility in endo-toxemic pigs but also increased ventricular afterloads, which ultimately is detrimental to cardiac function (H20). Possible sources of NO in the heart may be the vascular cells, the endothelial cells, and the cardiac myocytes (P6). 

Organ or tissue function Adrenergic Adrenergic response receptor Cholinergic response... 

Organ or Tissue Function Predominant Adrenoceptor Type Adrenergic Response Cholinergic Response"... 

Other authors showed that (R)a-methylhistamine, together with the inotropic and chronotropic adrenergic response from transmurally-stimulated atrial preparations, also inhibits the release of noradrenaline, thus providing direct evidence that histamine H3-receptors negatively modulate the cardiac sympathetic activity at a presynaptic site of action (Endou et al., 1994). In addition, it was demonstrated that (R)a-methylhistamine, at concentrations greater than 1 pM, produces further antiadrenergic activity by acting at inhibitory presynaptic a.2-adrenoceptors. This result is supported by the fact that yohimbine reverses this effect. 

The modulation of the N-type Ca2+ channels has been shown for some presynaptic receptors to be the mechanistic basis for the inhibition of Ca2+ influx [29]. In 1989 Takemura et al. [30] reported on the effective inhibition of histamine release from rat hypothalamic slices by the N-type Ca2+ -channel blocker ca-conotoxin. In addition Endou et al. [23] showed that to-conotoxin greatly potentiated the modulatory effect of (R)a-methylhistamine on cardiac adrenergic responses. Yang and Hatton [31] provided direct evidence for an H3 receptor-mediated modulation of ion permeability of neurons. They showed that in magnocellular histaminergic neurons from the rat posterior hypothalamus, H3... 

Pogwizd, S.M., Schlotthauer, K., Li, L., et al., 2001, Arrhythmogenesis and contractile dysfunction in heart failure Roles of sodium-calcium exchange, inward rectifier potassium current, and residual beta-adrenergic responsiveness. Circ Res., 88(11), pp 1159—67. 

The primary side effects associated with alpha-1-specific agonists are caused by excessive stimulation of alpha-adrenergic responses. Some of the more frequent side effects include increased blood pressure, headache, and an abnormally slow heart rate (because of reflex bradycardia). Some patients also report chest pain, difficulty breathing, and feelings of nervousness. These side effects are quite variable and are usually dose-related (i.e., they occur more frequently at higher doses). 

Canga L, Levi R, Rifkind AB. 1988. Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity Decreased -adrenergic responsiveness and evidence of increased intracellular calcium. Proc Natl Acad Sci USA 85 905-909. 

Simpson PJ. 1983. Norepinephrine stimulated hypertrophy of cultured rat myocardial cells is an alpha-1 adrenergic response. Clin Invest 72 732-738. 

Homey, C.J., Vatner, S.F., and Vatner, D.E. 1991. 3-adrenergic receptor regulation in the heart in pathophysiologic states abnormal adrenergic responsiveness in cardiac disease. Annu. Rev. Physiol. 53 137-159. 

Janssen, P.M., Schillinger, W., Donahue, J.K., Zeitz, O., Emami, S., Lehnart, S.E., Weil, J., Es-chenhagen, T., Hasenfuss, G., and Prestle, J. 2002. Intracellular p-blockade overexpression of Gai2 depresses the P-adrenergic response in intact myocardium. Cardiovasc. Res. 55 300-308. 

Sayar, K., Ugur, M., Gurdal, H., Onaran, O., Hotomaroglu, O., and Turan, B. 2000. Dietary selenium and vitamin E intakes alter p-adrenergic response of L-type Ca-current and P-adrenoceptor-adenylate cyclase coupling in rat heart. J. Nutr. 130 733-740. 

Relationship Between Redox Regulation and 3-Adrenergic Responses in the Heart... 

To provide further explanation for the underlying mechanisms on the depressed (3-adrenergic responses in both papillary muscle contractile activity and L-type Ca2+-currents, we investigated the state of coupling between p-AR, AC, and the density of p-ARs in the hearts of these Se groups. Basal AC activity of the membranes from the deficient group was lower than the control group, but the activity... 

Fig. 8.3 Effects of dietary selenium on p-adrenergic responses in rat heart, (a) L-type Ca2+ currents (I(a i recorded from ventricular myocytes with depolarization from —70mV to OmV, for 200 ms. Mean ( SEM) values of peak amplitudes of IcaL in both experimental and control groups. The cell capacitances of these three groups of cardiomyocytes were similar, (b) Average current-voltage relationships for peak IcaL (measured as the difference between the peak Ca2+ current and the end of 200-ms depolarization). The maximums of IcaL of both experimental groups were shifted to the right with respect to the control, (c) The threshold potentials were significantly more negative and activation potentials were more positive in both experimental groups with respect to the control. (Adapted from Sayar et al. 2000.)...

The effect of altered thyroid state on the activity of the /3-adrenergic receptor-adenylate cyclase complex have been documented in a number of cell types and tissues such as turkey erytrhrocytes, marrow cells, salivary glands, pancreatic cells, isolated hepatocytes, cardiac membranes and adipocytes. However changes in f3-adrenergic responsiveness do not occur in all cell types. 

The muscle cell 0-adrenergic responsiveness and the expression of myosin heavy chains... 

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