Cerebral vessels vasoconstriction

An early consequence of overexposure to PGDN is vasodilation of the cerebral vessels, which is the major factor in the development of headache. With more severe exposure, relaxation of the vascular smooth muscle can result in a fall in blood pressure followed by a compensatory vasoconstriction. 

Ergots acts as partial agonists at both alpha adrenoceptors and 5HT2 receptors in the vasculature and possibly in the CNS. Vasoconstrictive actions to decrease pulsation in cerebral vessels may be relevant to acute actions of ergotamine during migraine attack. 

Vasoconstriction —>X pulsation in cerebral vessels in migraine, especially if used in prodrome. Antagonists at alphaj receptors and partial agonists at both alpha I receptors and 5HT2 receptors. 

Vasoconstrictive actions to decrease pulsation in cerebral vessels may be relevant to acute actions of ergotamine during migraine attack. 

NIOSH-recommended exposure limits for NG, EGDN, or a mixture of the two were set at a level to prevent significant changes in the diameter of cerebral blood vessels during initial exposure, as indicated by the occurrence of headache or by decrease in blood pressure, thereby preventing the development of compensatory vasoconstrictive mechanisms that may eventually result in more serious effects. ... 

Xanthines (usually caffeine) are frequently combined with aspirin in the treatment of headaches. In combination with an ergot derivative, methylxanthines have been used to treat migraine. These effects are likely due to their ability to produce vasoconstriction of cerebral blood vessels. Aminophylline is useful in the rehef of pain due to acute biliary colic. 

Contrast-enhanced MRI with Gd-DTPA has been applied to the evaluation of several compounds in man, some focusing on the hemodynamic effects of the drugs on cerebral blood volumes. Kolbtisch and others compared the anesthetic agents nitrous oxide and sevofhirane, noting them to produce compound-specific patterns of diffuse increases in cerebral blood volume (Kolbitsch et al., 2001). Intravenous cocaine, on the other hand, was observed to produce dose-dependent vasoconstriction of cerebral blood vessels (Kaufman et ul., 1998). 

Intravenous administration of dopamine promotes vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels, via activation of Di receptors. Activation of the Di receptors in the renal vasculature may also induce natriuresis. The renal effects of dopamine have been used clinically to improve perfusion to the kidney in situations of oliguria (abnormally low urinary output). The activation of presynaptic D2 receptors suppresses norepinephrine release, but it is unclear if this contributes to cardiovascular effects of dopamine. In addition, dopamine activates Bj receptors in the heart. At low doses, peripheral resistance may decrease. At higher rates of infusion, dopamine activates vascular a. receptors, leading to vasoconstriction, including in the renal vascular bed. Consequently, high rates of infusion of dopamine may mimic the actions of epinephrine. 

Sumatriptan and the other triptans are selective agonists for 5-HT1D and 5-HT1B receptors the similarity of the triptan structure to that of the 5-HT nucleus can be seen in the structure below. These receptor types are found in cerebral and meningeal vessels and mediate vasoconstriction. They are also found on neurons and probably function as presynaptic inhibitory receptors. 

NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

Migraine headaches that do not respond to analgesics may be relieved by the use of an agonist of the 5-HT receptor, since these receptors are known to mediate vasoconstriction. Though the causes of migraine are not clear, they are characterized by dilation of cerebral blood vessels. 5-HTi agonists based on the 5-HT structure in current use include the sulphonamide derivative sumatriptan, and the more recent agents naratriptan, rizatriptan,... 

In addition to cardiac tissue, leptin receptors have also been identified in both cerebral and coronary vessels (Bjorbaek et al. 1997 Knudson et al. 2005). With respect to the latter it was proposed that OBR-mediated leptin-induced vasodilation occurs through an NO-dependent process and which was abolished by hyperleptinemia. This finding emphasizes the potential dual role of leptin on vascular tissue, a direct NO-dependent vasodilation and vasoconstriction occurring secondarily to central stimulation of the sympathetic nervous system. These effects will be discussed below in greater detail. 

Q7 The mechanisms which trigger migraine remain controversial. The underlying pathophysiology could be due to vasoconstriction of the cerebral arteries, causing transient ischaemia. This would be followed by compensatory vasodilation of the cerebral blood vessels to protect the ischaemic areas. This vasodilation may lead to an increase in intracranial pressure, which causes a severe headache. These events may be followed by changes in nerve activity and neurotransmitter levels. Inflammatory components are also likely to be involved in the pathology of this condition. 

In particular, an important role could be attributed to Y1 receptors in regulating the cardiovascular functions (Walker et al., 1991 Dermott et al., 1993). Through post-synaptic peripheral Y1 receptors, NPY, PYY and the selective Y1 receptor agonist, [Leu31,Pro34]NPY induced vasoconstriction in crucial areas, such as coronary and cerebral blood vessels, and even amplified the action of other vasoconstrictor agents like noradrenaline (Clarke etal., 1987 Edvinsson etal., 1987 Potter, 1988). 

Caffeine exerts a noticeable inotropic effect on the myocardium and a positive chronotropic effect particularly on the sinoatrial mode which ultimately result into a transient observed heart-rate, force of contraction, working of the heart, and above all the cardiac output. However, it is largely belived that the vasoconstriction of the cerebral blood vessels by caffeine remarkably contributes a lot to its exceptional capability to relieve headaches. 

Caffeine decreases peripheral resistance by direct vasodilatation and increases blood flow to a small extent. This effect results from the relaxation of smooth muscle of blood vessels. For coronary arteries, vasodilatation is also observed in vitro, but the effects of caffeine in human coronary arteries in vivo are unknown. Different effects of caffeine on circulation can be observed in different vascular beds and, for example, the treatment of migraine headaches by caffeine is mediated through the vasoconstriction of cerebral arteries. It has also been shown that caffeine is capable of attenuating postprandial hypotension in patients with autonomic failure. 

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