Depressor response

Endothelins exert widespread actions in the body. In particular, they cause dose-dependent vasoconstriction in most vascular beds. Intravenous administration of ET-1 causes a rapid and transient decrease in arterial blood pressure followed by a prolonged increase. The depressor response results from release of prostacyclin and nitric oxide from the vascular endothelium, whereas the pressor response is due to direct contraction of vascular smooth muscle. Endothelins also exert direct positive inotropic and chronotropic actions on the heart and are potent coronary vasoconstrictors. They act on the kidneys to cause vasoconstriction and decrease glomerular filtration rate and sodium and water excretion. In the respiratory system, they cause potent contraction of tracheal and bronchial smooth muscle. 

A single-bolus dose of the neuromuscular relaxants producing the delayed depressor response plus tachycardia (Paton 1957) is determined in each animal. This response being pathognomonic for histamine release is defined as sudden hypotension to less than 80 % of the control arterial pressure within 2 min of relaxant injection and with tachycardia to more than 25 % above the baseline value. 

The occurrence of histamine release is also treated as an all-or-none response to permit log-probit plotting. The delayed depressor response plus tachycardia is judged to have or have not occurred after each single bolus injection of the drugs. The percentage of animals responding at each dose level is then determined and the data handled by the Litchfield-Wilcoxon method. 

In vivo, intravenous administration of ET-1 to conscious [20], anaesthetized [21] or pithed [22] rats produces a biphasic blood pressure response a small, transient depressor response followed by a prolonged pressor response. The systemic blood pressure changes induced by ET-1 are reflected in changes in regional haemodynamics, although the dilator response is not seen in all vascular beds [23-25], Big ET-1, when administered intravenously, is almost as potent as ET-1 in producing a pressor response which suggests effective in vivo conversion to ET-1 [22]. The haemodynamic effects of ET-1 have also been studied in man and pressor responses are seen after intravenous or intra-arterial administration [26-28]. 

Isomannide contains two free hydroxyl groups the compound is easily nitrated, producing a white crystalline compound. This compound produces a reduction of the arterial tension in many species of animals and man. It was studied extensively by Krantz and associates and has had limited use in therapeutics. The hexanitrate of mannitol, the tetranitrate of erythritol, and glycerol trinitrate readily decompose when treated with dilute alkali. The dinitrate of isomannide is refractory to hydrolysis and by means of this, it was demonstrated that the depressor responses elicited by the nitrates of the sugar alcohols were due to the effect of their intact molecules and not to the products of hydrolytic cleavage and reduction. ... 

A similar study of the anti-hypertensive activity of the alkaloids of Kopsia teoi were also carried out which were also prompted by positive results from preliminary screening of alkaloidal extracts. The major aspidofractinine alkaloid kopsingine (191) was found to produce dose-related decreases in mean arterial blood pressure and heart rate in anaesthetized spontaneously hypertensive rats (SHR) which were similar to those elicited in normotensive controls. The same depressor response was shown by the 12-demethoxy derivative (kopsaporine, 192) and the semisynthetic 14,15-dihydto derivative of kopsingine 252, indicating that minor modifications to the basic structure of kopsingine do not significantly alter... 

Epinephrine reversal is a predictable result of the use of this agonist in a patient who has received an alpha-blocker. The term refers to a reversal in the blood pressure effect of moderate to large doses of epinephrine, from a pressor response (mediated by alpha-receptors) to a depressor response (mediated by pj-receptors) (Figure 10-2). The effect is not observed with phenylephrine or norepinephrine because these drugs lack p effects. 

In mice, both anandamide and synthetic carmabinoid receptor agonists cause biphasic hypotension (a depressor response, followed by a more sustained hypotensive phase but without a pressor component), which is thought to be entirely CB, receptor mediated, as the responses are absent in CB, receptor knockout mice (Ledent et al., 1999). 

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