Norepinephrine blood pressure response

In several papers the Kunos group has reported observations that may represent a starting point for novel medicinal chemistry research in this area [167, 168], Anandamide (i.v. bolus 4 mg/kg) caused a triphasic blood pressure response, brief hypotension, followed by a transient pressor and then a prolonged depressor phase. The hypotensive effect was not initiated in the CNS, but was due to a presynaptic action that inhibited norepinephrine release from sympathetic nerve terminals in the periphery (heart and vasculature). The inhibitory effect (but not the pressor effect) was antagonized by SR141716A, indicating that this peripheral action was mediated by CB receptors. 

The apparently linear relationship between biophase concentration and pharmacologic response usually reflects the fact that effects have been analyzed over only a limited concentration range (14). In many caseS/ an Ej ax model is required to analyze more pronounced effects/ such as the blood pressure response of cats to norepinephrine. This was the concentration-effect relationship initially analyzed by Segre (7) when he proposed a model for the time course of biophase concentrations. For the Ej ax model/ AE in Equation 19.8 is described by... 

Experimental studies in patients show that pretreatment with clonidine decreases the blood pressure response to small doses of dopamine does not affect the blood pressure response to noradrenaline (norepinephrine) and can increase the blood pressure responses to dobutamine, ephedrine, isoprenaline (isoproterenol) and phenylephrine. 

Horwitz D, Goldberg LI, Sjoerdsma A. Increased blood pressure responses to dopamine and norepinephrine produced by monoamine oxidase inhibitors in man. J Lab Clin Med (1960) 56, 747-53. 

The pressor (increased blood pressure) responses to tyramine and noradrenaline (norepinephrine) in depressed patients remained virtually unchanged after 14 days of treatment with mianserin 60 mg daily.In 5 healthy subjects taking maprotiline the pressor response to tyramine was reduced threefold while the noradrenaline response remained unchanged. ... 

Dopamine, norepinephrine, and serotonin have other responsibilities in the body besides dictating hunger. For example, norepinephrine also helps control blood pressure. Drugs that affect the level of these neurotransmitters interfere with other body processes and produce negative side effects. A drug that increases norepinephrine will decrease appetite, but... 

Pharmacology Bretylium tosylate inhibits norepinephrine release by depressing adrenergic nerve terminal excitability, inducing a chemical sympathectomy-like state. Bretylium blocks the release of norepinephrine in response to neuron stimulation. Peripheral adrenergic blockade causes orthostatic hypotension but has less effect on supine blood pressure. It has a positive inotropic effect on the myocardium. Pharmacokinetics Peak plasma concentration and peak hypotensive effects are seen within 1 hour of IM administration. However, suppression of premature ventricular beats is not maximal until 6 to 9 hours after dosing, when mean plasma concentration declines to less than 50% of peak level. Antifibrillatory effects occur within minutes of an IV injection. Suppression of ventricular tachycardia and other ventricular arrhythmias develops more slowly, usually 20 minutes to 2 hours after parenteral administration. 

In a normal resting subject who is receiving no drugs, there is a moderate parasympathetic tone to the heart, and sympathetic activity is relatively low. The ventricular muscle receives little, if any, parasympathetic innervation. As the blood pressure rises in response to norepinephrine, the baroreceptor reflex is activated, parasympathetic impulses (which are inhibitory) to the heart increase in frequency, and what little sympathetic outflow there is may be reduced. Heart rate is slowed so much that the direct effect of norepinephrine to increase the rate is masked and there is a net decrease in rate. Under the conditions described, however, the impact of the reflex on the ventricles is very slight because there is no parasympathetic innervation and the preexisting level of sympathetic activity is already low. A further decrease in sympathetic activity therefore would have little further effect on contractility in this subject. Thus, a decrease in heart rate and an increase in stroke volume will occur, and cardiac output will change very little. 

A slow intravenous injection of histamine produces marked vasodilation of the arterioles, capillaries, and venules. This causes a fall in blood pressure whose magnitude depends on the concentration of histamine injected, the degree of baroreceptor reflex compensation, and the extent of histamine-induced release of adrenal catecholamines. Vasodilation of cutaneous blood vessels reddens the skin of the face, while a throbbing headache can result from vasodilation of brain arterioles. Vasodilation is mediated through both Hj- and Hj-receptors on vascular smooth muscle. Stimulation of Hj-receptors produces a rapid and short-lived response, whereas stimulation of H2-receptors produces a more sustained response that is slower in onset. Stimulation of Hj-receptors on sympathetic nerve terminals inhibits the release of norepinephrine and its associated vasoconstriction. 

Postsynaptic Hj- and Hj-receptors are responsible for a variety of processes in the CNS. Hi-receptors mediate the maintenance of wakeful states, while Hj- and Hj-receptors participate in the regulation of blood pressure, body temperature, fluid homeostasis, and pain sensation. Presynaptic Hj-receptors serve as feedback inhibitors of the release of histamine, norepinephrine, and other neurotransmitters. 

Hypotensive activity. Essential oil, administered intravenously to dogs at a dose of 3 p,L/kg, was active. The ethanol (70%) extract, administered intravenously to dogs at a dose of 75 mg/kg, was active. There was a dip followed by rise in blood pressure° . Ethanol (80%) extract of the aerial parts, at a dose of 10 mg/kg, was not blocked by atropine. The extract did not inhibit pressor response of norepinephrine either . Ethanol (95%) extract of the seed, administered intravenously to dogs at a dose of 10 mg/kg, produced a transient effect that was blocked by atropine ". Petroleum ether fraction chromatographed and fraction eluted with chloroform, administered intravenously to rabbits at a dose of 0.80 mg/kg, was inactive. Methanol extract, administered intravenously to dogs and rabbits at a... 

Cardiovascular effect. [6]-shogaol, administered intravenously to rats at a dose of 0.5 mg/kg, produced a rapid fall in blood pressure, bradycardia, and apnea. There was a marked pressure pressor response in blood pressure that occurred after the rapid fall. A dose of 3.6 pM produced inotropic and chronotropic actions on isolated atria in rats. The effect disappeared by repeated injections or pretreatment of 100 mg/kg administered subcutaneously ° k Intravenous doses of 0.1 to 0.5 pg produced a pressor response in a dose dependent manner. The response was markedly reduced by spinal destruction at the sacral cord level. Norepinephrine (10 pg/kg, intravenously) induced pressor response that was not affected by spinal destruction. In rats in which the spinal cord was destroyed at the thoracic cord level, [6]-shogaol-induced pressor response was reduced by hexamethonium (10 mg/kg, intravenously) and phentolamine (10 mg/ kg, intravenously). When the spinal cord was destroyed at the sacral level, the pressor response was not affected by these blockades. In the hindquarters of rats that were perfused with rat s blood, [6]-shogaol produced two pressor responses on the perfusion pressure. The first was accompanied by a rise in systemic blood pressure, was re-... 

Figure 2.1 Fear responses involve the activation of many brain areas. The hypothalamus controls physical changes in the body, such as increased blood pressure and dilated pupils. The central gray area causes freezing behavior, the reticular net triggers a reflex response, and norepinephrine increases attention.

The direct slowing of sinoatrial rate and atrioventricular conduction that is produced by muscarinic agonists is often opposed by reflex sympathetic discharge, elicited by the decrease in blood pressure (see Figure 6-7). The resultant sympathetic-parasympathetic interaction is complex because muscarinic modulation of sympathetic influences occurs by inhibition of norepinephrine release and by postjunctional cellular effects. Muscarinic receptors that are present on postganglionic parasympathetic nerve terminals allow neurally released acetylcholine to inhibit its own secretion. The neuronal muscarinic receptors need not be the same subtype as found on effector cells. Therefore, the net effect on heart rate depends on local concentrations of the agonist in the heart and in the vessels and on the level of reflex responsiveness. 

It is possible to circumvent compensatory responses that may partially cancel the primary effect in the intact organism for example, the heart rate-increasing action of norepinephrine cannot be demonstrated in the intact organism because a simultaneous rise in blood pressure elicits a counterregulatory reflex that slows cardiac rate. 

Norepinephrine Mostly excitatory, but inhibitory in some areas. Secreted by neurons in the locus ceruleus (subcortical area) to widespread areas of the brain, controlling wakefulness, overall activity, and mood. Also diffusely secreted in the sympathetic nervous system. Diffuse and widespread symptoms, including depression, changes in blood pressure, heart rate, and diffuse physiological responses, among many others. An important transmitter in the sympathetic branch of the autonomic nervous system. Diffusely affected by many medications. Several antidepressants work specifically on this neurotransmitter and its receptor sites. Many medications for general medical conditions affect this neurotransmitter as well. 

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