Norepinephrine-induced Hypertension Research Articles

Effect of a Permanent Magnetic Field on Blood Pressure Regulation

We investigated the influence of a permanent magnetic field (PMF) on the carotid sinus region in rabbits during hypertension caused by nor-epinephrine infusion. The experiments were carried out under pentobarbital anesthesia, and blood pressure, heart rate and respiration were monitored. The PMF significantly decreased blood pressure during norepinephrine-induced hypertension. PMF might stabilize cellular membranes, leading to an increase of buffer capacity of the sinocarotic baroreceptors to blood-pressure alterations.

Cerebrovascular permeability to horseradish peroxidase in hypertensive rats: effects of unilateral locus ceruleus lesion

Unilateral locus ceruleus lesion enhances leakage of radioiodinated human serum albumin into the ipsilateral cerebral cortex of rats with norepinephrine-induced hypertension. This ultrastructural study was undertaken, to determine the mechanism by which this permeability alteration occurs, using horseradish peroxidase (HRP) as a tracer. Unilateral locus ceruleus lesion was produced in male Wistar-Furth rats by stereotaxic microinfusion of 5 micrograms of 6-hydroxydopamine. Two weeks later, rats were injected with HRP intravenously and acute hypertension was induced in awake rats by an intravenous infusion of norepinephrine (6 micrograms), epinephrine (6 micrograms) or angiotensin amide (12 micrograms) given over a 2-min period. Thirty seconds later, the rats were perfused with fixative under deep anesthesia and their brains were sliced and processed for demonstration of HRP reaction product. Leakage of HRP occurred in both cerebral hemispheres in response to hypertension induced by the three pressor agents, but the leakage was greater on the lesioned side in response to epinephrine and norepinephrine, while in the case of angiotensin-induced hypertension side-to-side differences in permeability alterations were not observed. In both cerebral hemispheres increased permeability affected mainly arterioles, which showed enhanced pinocytosis as the principal mechanism of HRP extravasation.

Effects of nicardipine on the systemic and renal hemodynamics in acutely elevated blood pressure induced by vasoactive agents in conscious rabbits.

The effects of the calcium antagonist, nicardipine, on blood pressure and renal hemodynamics were examined in rabbits with norepinephrine- and angiotensin II-induced elevation of blood pressure. With norepinephrine-infusion, the mean arterial pressure increased from 84 +/- 4 to 118 +/- 4 mmHg accompanied by decreases in heart rate (10%) and renal blood flow (45%). In contrast to the changes in renal blood flow with norepinephrine-infusion, renal blood flow following angiotensin II-induced elevation of blood pressure was decreased by more than 60% at the same degree of elevation of mean arterial pressure. Both intravenous and intrarenal administration of nicardipine (1 microgram/kg) reduced the mean arterial pressure and restored the decreased heart rate and renal blood flow in both norepinephrine- and angiotensin II-infused animals. Intrarenal injection of nicardipine decreased the elevated mean arterial pressure of angiotensin II-induced hypertension more than did intravenous injection (16 +/- 2 vs. 11 +/- 3 mmHg, p less than 0.05). Renal nerve denervation did not lead to any significant effects on the mean arterial pressure, heart rate and renal blood flow following intravenous or intrarenal injection of nicardipine in norepinephrine-infused animals. On the other hand, in angiotensin II-induced elevation of blood pressure, the potentiated hypotensive effect of intrarenal injection of nicardipine was lost in renally denervated animals. In conclusion, the calcium antagonist, nicardipine, was shown to reduce the acutely elevated blood pressure caused by norepinephrine or angiotensin II. In angiotensin II-induced elevation of blood pressure, the renal vasculature may play a more important role in both pressor and depressor aspects in the regulation of blood pressure as compared to its role in norepinephrine-induced hypertension.

The protective influence of the locus ceruleus on the blood-brain barrier.

The functions of the putative noradrenergic innervation of cerebral microvessels from the nucleus locus ceruleus remain ambiguous. Although most evidence indicates that such innervation does not have a major role in the control of cerebral blood flow, there are increasing indications that it modulates transport and permeability functions of the blood-brain barrier. In this study we investigated the effect of unilateral chemical lesioning of the locus ceruleus on the leakage of radioiodinated human serum albumin across the blood-brain barrier. Experiments were performed in awake and restrained rats under steady-state conditions and during drug-induced systemic arterial hypertension, and in anesthetized and paralyzed rats during bicuculline-induced seizures. Both hypertension and seizures are known to be associated with increased leakage of macromolecules across the blood-brain barrier. Albumin leakage into norepinephrine-depleted forebrain structures ipsilateral to the locus ceruleus lesion was compared with that of the contralateral side. There were no side-to-side differences in blood-brain barrier permeability to albumin under steady-state conditions, the stress of restraint, or angiotensin-induced hypertension, or after isoproterenol administration. Norepinephrine-induced hypertension and seizures, however, caused significant increases in albumin leakage into forebrain structures ipsilateral to the lesion. These results suggest that noradrenergic innervation of cerebral microvessels from the locus ceruleus helps preserve the integrity of the blood-brain barrier during pathophysiological states associated with hypertension and increased circulating catecholamines.

Hypotensive activity of PAF-acether in rats.

PAF-acether caused a dose-related decrease in blood pressure of conscious SHR rats (5–20 μg/kg i.p.) and anaesthetized normotensive rats (0.06–0.50 μg/kg i.v.). In anaesthetized normotensive rats, PAF-acether-induced hypotension was not associated with tachycardia and not modified by various pretreatments such as atropine, mepyramine, cimetidine, propranolol, sulpiride, ketoprofen (an inhibitor of prostaglandin cyclooxygenase) and teprotide. PAF-acether (0.5 μg/kg i.v.) reduced the pressor effect of norepinephrine but not that of angiotensine II. In pithed rats, PAF-acether (0.12–0.50 μg/kg i,.v.) shifted the dose-response curve for norepinephrine-induced hypertension to the right in a parallel manner and did not reverse the inhibitory action of clonidine on cardiac nerve stimulation. These results suggest that the hypotensive effect of PAF-acether in anaesthetized rats may be mediated by α-adrenergic blockade and PAF-acether looks like a powerful postsynaptic adrenoceptor blocking agent. However,in vitro, up to 100 μg/l, PAF-acether did not modify the norepinephrine-induced contractions on non-vascular (vas deferens) and vascular (thoracic aorta) preparations of rats. Moreover, PAF-acether did not inhibitin vitro [3H]WB-4101 and [3H]p-aminoclonidine binding in rat brain preparations. This absence ofin vitro activity suggest that thein vivo adrenolytic activity of PAF-acether is in fact an indirect one either via a directly active metabolite or possibly through the release of an unidentified endogenous adrenolytic factor.

Role of the pressor action of angiotensin II in experimental hypertension.

Experiments with rabbit aortic strips and pithed rats indicated that 1-Sar-8-Ala-angiotensin II (Sar-Arg-Val-Tyr-Val-His-Pro-Ala) is a specific competitive antagonist of the vascular action of angiotensin II. Norepinephrine-induced hypertension was not affected by infusions of 1-Sar-8--Ala-angiotensin II which evoked a dose-related reduction of angiotensin II-induced hypertension in conscious rats. Infusions of 1-Sar-8-Ala-angiotensin II that caused a dose-related reduction of the blood pressure of conscious rats in the acute phase of unilateral renal hypertension were ineffective during the chronic phase of such hypertension. Infusions of 1-Sar-8-Ala-angiotensin II lasting 1 hour did not reduce the blood pressure of normotensive, spontaneously hypertensive, or metacorticoid hypertensive conscious rats. These data indicate that, under certain experimental conditions, the blood pressure of rats during the acute phase of unilateral renal hypertension is maintained hy the endogenous angiotensin II previously demonstrated to he present in the plasma in supernormal concentrations. The blood pressure of normotensive, spontaneously hypertensive, metacorticoid hypertensive, and chronic unilateral renal hypertensive rats previously shown to have normal plasma levels of renin and angiotensin II appeared to be independent of the pres.sor action of endogenous angiotensin II. This is additional direct evidence implicating the pressor action of angiotensin II in the etiology of renal hypertension.

Electrocardiographic changes during norepinephrine-induced hypertension in normal man

The electrocardiographic alterations occurring in normal males during norepinephrine-induced hypertension, before and after the administration of atropine sulfate, are reported. The possible mechanisms of the observed changes are discussed, but no specific conclusions can be reached. Further studies are indicated which may help to elucidate the mechanism of formation of the electrocardiographic “acute strain” pattern. It will be necessary to dissociate the direct myocardial effects of norepinephrine from its hypertensive action and from the marked reflex vagal stimulation which it produces. Since norepinephrine probably plays a significant role under conditions of stress, our results indicate that fluctuations in the contour of the electrocardiogram may at times be explained by norepinephrine secretion.