Hypertensive responses

Phenylephrine. Phenylephrine hydrochloride is an a -adrenoceptor agonist. Phenylephrine produces powerful vasoconstrictor and hypertensive responses. This results in baroreceptor activation of a reflex bradycardia and thus is useful in the treatment of supraventricular tachyarrhythmias. Unlike epinephrine [51-43-4] the actions of which are relatively transient, phenylephrine responses are more sustained (20 min after iv dosing and 50 min after subcutaneous dosing) (86). 

Taken together with the results obtained by DlPalma s group,117,118 the finding by Barnes et al.H 0f the particularly large effect of prior treatment with reserplne on the response of the arterial pressure to I seems to confirm the Involvement of catecholamine release In this hypertensive response. It Is clear, however, that X also has a direct Inotropic effect on the heart, In that the increase In stroke volume was blocked only partially by any of the three possible antagonists used by Barnes et al. Xn view of the fact that none of the possible antagonists was able to prevent more than about 68.52 of the increase In peripheral resistance Induced by X, this oxime may well have direct stimulant effects on vascular smooth muscle. 

Infusion of II at 45 mg/kg into one subject resulted in a hypertensive response Immediately after the infusion was completed.154 Oral doses of 2 and 4 g of II had no detectable effect on blood pressure in another subject. 

Whereas the most striking cardiovascular response to the monopyridinlum monoxlmes is hypertension, that to the blspyrldinlum blsoxlmes 1b prolonged hypotension after an Initial, short hypertensive response. The hypertension and tachycardia that have been induced by initial... 

Calesnlck, B., Christensen, J.A., Canby, P. 1964. Hypertensive response produced by the Intravenous administration of 1-methyl-pyrldinlum-2-aldaxime chloride (2-FAM Cl). J. New Drugs 4 221-222. 

Increase in hypertensive response after seizure induction... 

Increased norepinephrine stored in adrenergic neuron. Displacement of these stores by other drugs may produce acute hypertensive response. MAOIs have intrinsic hypoglycemic activity. 

The effects of topical dexamethasone on intraocular pressure have been compared with those of fluorometho-lone (SEDA-22, 446 66). The ocular hypertensive response to topical dexamethasone in children occurs more often, more severely, and more rapidly than that reported in adults. It should be avoided in children if possible and it is desirable to monitor the intraocular pressure when it is being used. Fluorometholone may be more acceptable. 

Children have more frequent, more severe, and more rapid ocular hypertensive responses to topical dexamethasone than adults. In one case a systemic glucocorticoid caused significant but asymptomatic ocular hypertension in a child (67). 

The ocular hypertensive response in this case could have been due to systemic absorption of glucocorticoid through the skin of the eyelid, especially when there was a surgical wound. Alternatively, a sufficient amount of ointment could have seeped over the eyelid margins, causing the rise in intraocular... 

Chua JK, Fan DS, Leung AT, Lam DS. Accelerated ocular hypertensive response after application of corticosteroid ointment to a child s eyelid. Mayo Clin Proc 2000 75(5) 539. 

In parallel with animal experiments, Vane and colleagues (89) showed that intravenous teprodde reduced the pressor activity of angiotensin I in humans. Nor was there any significant augmentation or reduction of angiotensin II s hypertensive response. A biochemical proof of efficacy had been achieved, and clinical antihypertensive studies were begun. 

SYMPATHOMIMETICS H2 RECEPTOR BLOCKERS t efficacy and adverse effects of sympathomimetics Unclear t hypertensive response dose reduction may be required. Monitor ECG for tachycardias... 

A number of studies suggest that supplements of vitamin Bg may have a hypotensive action. Supplements of300 mg of vitamin Bg per kg of body weight per day attenuated the hypertensive response of rats treated with deoxycorticosterone acetate (Fregly and Cade, 1995). At a more realistic level of supplementation (five times the usual amount provided in the diet), vitamin Bg prevented the development of hypertension in the Zucker fa/fa) obese rat. Withdrawal of the vitamin supplement led to the development of hypertension (Lai et al., 1996). 

Platelet-activating factor or l-alkyl-2-acetyl- n-glycero-3-phosphocholine is an ether analog of phosphatidylcholine. This biologically active lipid is of great current interest. Initially, it was found to affect aggregation of platelets and to induce a hypertensive response at very low concentrations. Recent research has revealed its role as a mediator of inflammation and of other physiologic effects on many different types of cells. 

Brain TP receptors, shown to be present in both animal (37,38) and human (38,39) hrain tissues, were found to mediate calcium mobilization (38) and a hypertensive response in rats that was partially attributed to the release of arginine vasopressin (40). 

Mice lacking the oqB-adrenergic receptor were generated by the Cotecchia lab in 1997 (76). Whereas basal blood pressure was not altered in these animals, the hypertensive response to oq-agonists was significantly blunted. Subsequently, the a1A- (77) and a1D-knockouts (78) were generated. All three oq-subtypes play important roles in the cardiovascular system, and the oqB may be particularly important in the central nervous system (reviewed in ref. 79) (see Chapter 8). 

D Located in brain and arteries (aorta, coronary, mesenteric) Maintain resting BP Vasopressor and hypertensive responses Coronary vasoconstriction... 

Agents acting via oq-ARs to elicit changes in blood pressure induce a characteristic biphasic hemodynamic profile an initial, transient hypertensive response (by which peripherally located arterial oq-ARs constrict vascular smooth muscle) is followed by a longer-lived, centrally mediated attenuation of sympathetic outflow (culminating in a sustained drop in blood pressure). For this reason, oq-AR agonists are used to treat high blood pressure in some populations of hypertensive patients. 

As discussed above, agents acting via o -ARs to elicit changes in blood pressure induce a characteristic biphasic hemodynamic profile consisting of a transient hypertensive response followed by the sustained, centrally localized o -AR-mediated drop in blood pressure. As with the a2A-AR, mice null for the o ij-AR (a2B-AR / ) have documented the role of the a2B-AR subtype in modulating the pressor, or increased, blood pressure responses following a2-agonist activation of peripheral mechanisms (11). Control studies demonstrated that a2B-... 

Gavras H, Bain GT, Bland L, Vlahakos D, Gavras I. Hypertensive response to saline microinjection in the area of the nucleus tractus solitarii of the rat. Brain Res 1985 343 113-119. 

B Abolished hypertensive response to a2-agonists (60) X Hypertension after nephrectomy and salt loading (62)... 

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