Norepinephrine vasoconstrictor effect

Vasopressin is a peptide hormone produced by the hypothalamus and secreted by the posterior pituitary in response to stimulation. Normal stimuli for vasopressin release are hyperosmolarity and hypovolemia, with thresholds for secretion of greater than 280 mOsm/kg and greater than 20% plasma volume depletion. A number of other stimuli, such as pain, nausea, epinephrine, and numerous drugs, induce release of vasopressin. Vasopressin release is inhibited by volume expansion, ethanol, and norepinephrine. The physiological effect of vasopressin is to promote free water clearence by altering the permeability of the renal collecting duct to water. In addition, it has a direct vasoconstrictor effect. Consequently, vasopressin results in water retention and volume restoration. In patients with septic shock, vasopressin is appropriately secreted in response to hypovolemia and to elevated serum osmolarity (R14). 

Drug Y caused a marked increase in diastoUc pressure, suggesting strong alpha vasoconstrictor effects. It also caused a moderate increase in pulse pressure, suggesting some beta-agonist action. The drug that best matches this description in norepinephrine. The answer is (E). 

Serotonin is found not only in the brain but also in storage vesicles within circulating blood platelets. It has both vasodilator and vasoconstrictor effects. If the vascular endothelium is intact, 5-HT released from platelets causes vasodilatation, related to the release of nitric oxide. It can cause vasodilatation by inhibiting the release of norepinephrine. If the vascular endothelium is damaged, 5-HT causes vasoconstriction, and it amplifies the effect of other vasoactive substances, such as histamine, angiotensin II, and norepinephrine. Coronary blood flow is decreased by the release of 5-HT from circulating platelets, especially when the coronary vessels are damaged. 

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

The endogenous release of the potent vasoconstrictor neuropeptide Y (NPY) is increased during sepsis and the highest levels are detected in patients with shock (A8). NPY is a 36-amino-acid peptide belonging to the pancreatic polypeptide family of neuroendocrine peptides (T2). It is one of the most abundant peptides present in the brain and is widely expressed by neurons in the central and peripheral nervous systems as well as the adrenal medulla (A3). NPY coexists with norepinephrine in peripheral sympathetic nerves and is released together with norepinephrine (LI9, W14). NPY causes direct vasoconstriction of cerebral, coronary, and mesenteric arteries and also potentiates norepinephrine-induced vasoconstriction in these arterial beds (T8). It appears that vasoconstriction caused by NPY does not counterbalance the vasodilatator effects of substance P in patients with sepsis. The properties of vasodilatation and smooth muscle contraction of substance P are well known (14), but because of the morphological distribution and the neuroendocrine effects a possible stress hormone function for substance P was also advocated (J7). Substance P, which is a potent vasodilatator agent and has an innervation pathway similar to that of NPY, shows a low plasma concentration in septic patients with and without shock (A8). 

Effects of vasodilators on contractions of human vein segments studied in vitro. A shows contractions induced by two vasoconstrictor agents, norepinephrine (NE) and potassium (K+). shows the relaxation induced by nitroglycerin (NTG), 4 P-mol/L. The relaxation is prompt. C shows the relaxation induced by verapamil, 2.2 it-mol/L. The relaxation is slower but more sustained. 

Cocaine differs from the other local anesthetics with respect to its cardiovascular effects. Cocaine s blockade of norepinephrine reuptake results in vasoconstriction and hypertension, as well as cardiac arrhythmias. The vasoconstriction produced by cocaine can lead to local ischemia and, in chronic abusers who use the nasal route, ulceration of the mucous membrane and damage to the nasal septum have been reported. The vasoconstrictor properties of cocaine can be used clinically to decrease bleeding from mucosal damage or surgical trauma in the nasopharyneal region. 

Epinephrine [ep ee NEF rin] is one of five catecholamines—epinephrine, norepinephrine, dopamine, dobutamine, and isoproterenol—commonly used in therapy. The first three catecholamines occur naturally, the latter two are synthetic compounds (see Figure 6.7). Epinephrine is synthesized from tyrosine in the adrenal medulla and released, along with small quantities of norepinephrine, into the blood stream. Epinephrine interacts with both a and p receptors. At low doses, p effects (vasodilation) on the vascular system predominate, whereas at high doses, a effects (vasoconstrictor) are strongest. 

Correct answer = D. Reserpine blocks the uptake of norepinephrine into intracellular storage vesicles, resulting in depletion of norepinephrine and gradual decline in blood pressure. Phenylephrine is a pure vasoconstrictor and raises systolic and diastolic blood pressures. Dopamine raises systolic and diastolic blood pressures by stimulating the heart and (at high doses) causing vasoconstriction. Ephedrine raises systolic and diastolic blood pressures by vasoconstriction and cardiac stimulation. Norepinephrine has a pressor effect. 

To ensure a reasonably long-lasting local effect with minimal systemic action, a vasoconstrictor (epinephrine, less frequently norepinephrine or vasopressin derivatives) is often co-administered in an attempt to confine the drug to its site of action. As blood Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

Cocaine (alkaloid) is used medicinally solely as a surface anaesthetic (for abuse toxicity, see p. 192) usually as a 4% solution, because adverse effects are both common and dangerous when it is injected. Even as a surface anaesthetic sufficient absorption may take place to cause serious adverse effects and cases continue to be reported only specialists should use it and the dose must be checked and restricted. Cocaine prevents the uptake of catecholamines [adrenaline (epinephrine), noradrenaline (norepinephrine)] into S5nnpathetic nerve endings, thus increasing their concentration at receptor sites, so that cocaine has a built-in vasoconstrictor action, which is why it retains a (declining) place as a... 

Cocaine is a potent CNS stimulant that elicits a state of increased alertness and euphoria with its actions similar to those of amphetamine but of shorter duration. These CNS effects are thought to be largely associated with the ability of cocaine to block dopamine reuptake at nerve synapses and thereby prolong the action of dopamine in the CNS. It is this response that leads to recreational abuse of cocaine. Cocaine also blocks the reuptake of norepinephrine at presynaptic nerve terminals this produces a sympathomimetic response (including an increase in blood pressure, heart rate, and body temperature). Cocaine is effective as a local anesthetic and vasoconstrictor of mucous membranes and is therefore used clinically for nasal surgery, rhinoplasty, and emergency nasotracheal intubation. 

Postsynaptic a-adrenoceptors have been characterized in afferent and efferent arterioles isolated from rabbit renal cortex [263]. In both the afferent and efferent arteriole selective a 1-adrenoceptor agonists produced concentration-dependent vasoconstrictor responses with the maximum responses being equal to that of norepinephrine. Selective a 2-receptor agonists had less of an effect. The a 1-receptor antagonist, prazosin, produced a rightward shift in the concentration-response curve to norepinephrine, while the selective a 2-receptor antagonist, rauwolscine had no... 

Surgical patients who are premedicated with chlorpromazine respond poorly to pressor drugs, requiring larger-than-anticipated doses. The inotropic effects of epinephrine (increase in the strength of muscular contraction) are reduced by chlorpromazine. The chronotropic effects of epinephrine (increase in the rate of contraction) are increased as the result of chlorpromazine s anticholinergic properties. The local vasoconstrictor action of epinephrine (as used with a local anesthetic) is blocked by chlorpromazine, but its hyperglycemic effect is not. The lethal effect of toxic doses of epinephrine or norepinephrine can be reversed by chlorpromazine. 

---