Supersensitivity to the stimulant action of noradrenaline on human myometrium near term

Noradrenaline (10-50 nM) and tyramine (0.05-1 mM) enhanced contractile force elicited by field stimulation of strips of myometrium from non-pregnant and pregnant women. In higher concentrations, noradrenaline produced sustained contractions. The EC50 values for noradrenaline were 0.4 microM in tissues from pregnant women and 3.1 microM in tissues from non-pregnant women; maximum responses were greater in the former tissues. In addition, the effects of noradrenaline on myometrium from pregnant women were more marked on the inner layer than on the outer layer, antagonized by the alpha 1-adrenoceptor antagonist prazosin (0.1 and 1.0 microM), and unaffected by the inhibitor of neuronal uptake, nisoxetine (0.1 microM). Taken together, these observations confirm that supersensitivity to noradrenaline develops during pregnancy and is present near term. The supersensitivity to noradrenaline at term can be attributed only in part to a decrease in its removal by the sympathetic innervation, which declines towards term, because responses to tyramine were also enhanced in tissues from pregnant women. It is possible that gap junction formation may also contribute to this supersensitivity.

Cerebrovascular reactivity to noradrenaline and serotonin following experimental subarachnoid hemorrhage

✓ This study analyzes the time course of the changes induced by subarachnoid hemorrhage (SAH) in the sensitivity of cat cerebral arteries to noradrenaline and serotonin. Cerebral arteries displayed a supersensitivity to these amines, which was most marked 3 days after the experiment and then gradually disappeared. The supersensitivity to serotonin was greater and longer than the response to noradrenaline. The increased in the vascular contractile response induced by SAH was similar to that seen after superior cervical ganglionectomy or intracisternal injections of 6-hydroxydopamine. It is suggested that supersensitivity to noradrenaline and serotonin induced by SAH may be involved in the production of chronic cerebral vasospasm.

Modulation of Sympathetic Vascular Tone by Prostaglandins in Corticosterone-Induced Hypertension in Rats

1. In corticosterone-induced hypertension in rats the activity of the peripheral sympathetic nervous system and its modulation by prostaglandins was studied. 2. Plasma concentrations of noradrenaline were reduced if compared with those in normotensive control rats. 3. The sensitivity of the isolated perfused hindlimb preparation to noradrenaline was enhanced before blood pressure rose and increased further with the development of hypertension. 4. Arachidonic acid, prostacyclin (prostaglandin I2), but not 6-keto-prostaglandin F1α, reversed the supersensitivity to noradrenaline. 5. These results suggest that corticosterone induces a supersensitivity to noradrenaline by inhibiting the biosynthesis of prostaglandins. Changes in the sensitivity of the vascular smooth muscle may play a role in the development of glucocorticoid hypertension.