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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of ischemic deficits caused by vasospasm relies on enhancing cardiac output, inducing arterial hypertension, and expanding the intravascular volume in an attempt to improve CBF. Different treatment protocols exist from institution to institution to achieve these goals. The role of calcium-channel blockers now is well established. The newest focus on prevention of vasospasm includes tPA and a variety of anti-inflammatory drugs and potential neuroprotective drugs under research. Endovascular therapy for vasospasm has an increasing role in treating patients who are unable to tolerate induced hypertension or aggressive volume augmentation. We will return to our index case of the 63-year-old woman with SAH caused by an ACoA aneurysm to review some major management issues. After placing a ventriculostomy and slowly lowering ICP, the patient became alert and was fully oriented. She had aneurysm surgery on hospital day 2, with an uncomplicated immediate postoperative course. A Swan-Ganz catheter, placed for intraoperative monitoring, was kept in place and she was hydrated with 125 mL/hour of normal saline, achieving a PAWP of 10 to 16 mm Hg. Her mean arterial blood pressure without pharmacologic intervention was 95 to 110 mm Hg. She had continued clinical improvement with resolution of her left hemiparesis. On hospital day 5, her ventriculostomy was clamped because cerebrospinal fluid drainage was minimal. The following morning, the patient was arousable only to deep pain and her left side was flaccid. An emergent CT scan demonstrated no new hemorrhage, no increase in ventricular size, and no infarct. Vasospasm was considered the most likely cause. Hypertensive therapy was about to be initiated with a phenylephrine drip, but within an hour she was fully alert and moving all extremities equally. A search for other potential causes of neurologic decline was undertaken and revealed a phenytoin level of 5.5. It was thought that the patient most likely had had a seizure and that her clinical deterioration represented a postictal state. She received a bolus infusion of phenytoin. On hospital day 7, the patient became confused, insisting that her nurse was her son and ordering him out of her "apartment." Lower extremity weakness was detected. CT scan was unchanged. Phenylephrine was started but she developed precordial lead ST elevation and elevated cardiac enzymes. Topical nitrate therapy was initiated and phenylephrine was discontinued. The patient underwent emergent cerebral angiography, which demonstrated moderate to severe bilateral ACA spasm and moderate right MCA spasm.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Management of aneurysmal subarachnoid hemorrhage. 747 15

In this study we infused phenylephrine into adult Wistar rats and used losartan to test for a possible role of angiotensin II in the phenylephrine-induced fibrosis. Phenylephrine, given by Alzet minipumps at a rate of 25 mg.kg-1.d-1, produced a rapid and striking fibrotic response that was obvious after 1 day and progressed throughout a 3-day infusion period. Northern and Western blot analyses showed large increases in cardiac fibronectin expression and atrial natriuretic peptide mRNA, corresponding to fibroblast proliferation and myocyte hypertrophy, respectively. Cardiac fibrosis, fibronectin mRNA, and atrial natriuretic peptide mRNA were blocked by prazosin (7 mg.kg-1.d-1). Administration of losartan (10 mg.kg-1.d-1) resulted in a threefold decrease in interstitial and perivascular fibroblast proliferation, as measured by proliferating cell nuclear antigen immunoreactivity (p < .05), a marked reduction of fibronectin mRNA in the heart, and a moderate reduction of cardiac atrial natriuretic peptide mRNA. The data suggest that effects mediated by a1-adrenergic and angiotensin type 1 receptors may promote cardiac fibrosis.
Hypertension 1995 Apr
PMID:Effect of angiotensin II blockade on the fibroproliferative response to phenylephrine in the rat heart. 753 16

The purpose of this study was to compare two anaesthetic protocols for haemodynamic instability (heart rate (HR) or mean arterial pressure (MAP) < 80 or > 120% of ward baseline values) measured at one-minute intervals during carotid endarterectomy (CEA). One group received propofol/alfentanil (Group Prop; n = 14) and the other isoflurane/alfentanil (Group Iso; n = 13). Periods of haemodynamic instability were correlated to episodes of myocardial ischaemia as assessed by Holter monitoring (begun the evening before surgery and ceasing the morning of the first postoperative day). In Group Prop, anaesthesia was induced with alfentanil 30 micrograms.kg-1 i.v., propofol up to 1.5 mg.kg-1 and vecuronium 0.15 mg.kg-1, and maintained with infusions of propofol at 3-12 mg.kg-1.hr-1 and alfentanil at 30 micrograms.kg-1.hr-1. In Group Iso, anaesthesia was induced with alfentanil and vecuronium as above, thiopentone up to 4 mg.kg-1 and maintained with isoflurane and alfentanil infusion. Phenylephrine was infused to support MAP at 110 +/- 10% of ward values during cross-clamp of the internal carotid artery (ICA) in both groups. Emergence hypertension and/or tachycardia was treated with labetalol, diazoxide or propranolol. Myocardial ischaemia was defined as ST-segment depression of > or = 1 mm (60 msec past the J-point) persisting for > or = one minute. For the entire anaesthetic course (induction to post-emergence), there was no difference between groups for either duration or magnitude outside the < 80 or > 120% range for HR or MAP. However, when the period of emergence from anaesthesia (reversal of neuromuscular blockade to post-extubation) was assessed, more patients were hypertensive (P = 0.004) and required vasodilator therapy in Group Iso (10/13 vs 5/14; P = 0.038 Fisher's Exact Test). The mean dose of labetalol was greater in Group Iso (P = 0.035). No patient demonstrated myocardial ischaemia during ICA cross-clamp. On emergence, 6/13 patients in Group Iso demonstrated myocardial ischaemia compared with 1/14 in Group Prop (P = 0.029). Therefore, supporting the blood pressure with phenylephrine, during the period of ICA cross-clamping, appears to be safe as we did not observe any myocardial ischaemia at this time. During emergence from anaesthesia, haemodynamic instability was associated with myocardial ischaemia. Under these specific experimental conditions, with emergence, hypertension and myocardial ischaemia were more prevalent with more frequent pharmacological interventions in patients receiving isoflurane.
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PMID:Haemodynamic instability and myocardial ischaemia during carotid endarterectomy: a comparison of propofol and isoflurane. 755 93

The goal of this study was to determine the role of nitric oxide in disruption of the blood-brain barrier during acute hypertension. We examined the microcirculation of the cerebrum in vivo. Permeability of the blood-brain barrier was quantitated by the formation of venular leaky sites and clearance of fluorescent-labeled albumin (FITC-albumin) before and during phenylephrine-induced acute hypertension. We compared disruption of the blood-brain barrier during acute hypertension in untreated rats and in rats treated for 1 h with topical application of NG-monomethyl-L-arginine (L-NMMA; 100 microM) or NG-nitro-L-arginine methyl ester (L-NAME; 100 microM). Under control conditions, no venular leaky sites were visible and clearance of FITC-albumin was minimal in untreated rats and in rats treated with topical application of nitric oxide synthase inhibitors. Phenylephrine (20 micrograms/kg/min for 5 min) infusion increased systemic arterial pressure by a similar magnitude in all groups of rats and produced disruption of the blood-brain barrier in venules. However, the magnitude of disruption of the blood-brain barrier during acute hypertension was significantly less in rats treated with L-NMMA (52% reduction in the clearance of FITC-albumin) and L-NAME (47% reduction in clearance of FITC-albumin). The findings of the present study suggest that synthesis/release of nitric oxide contributes to disruption of the blood-brain barrier during acute hypertension.
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PMID:Role of nitric oxide in disruption of the blood-brain barrier during acute hypertension. 758 77

We previously demonstrated that intra-arterial infusion of insulin attenuates vasoreactivity to phenylephrine and angiotensin II in the forearm of normotensive humans, which suggests that the pressor effects of insulin via sympathetic activation may be offset in peripheral arteries. In the present study, we investigated the effects of insulin on vasoreactivity in hypertensive humans. Seven male patients with essential hypertension (age, 26 +/- 2 yr; blood pressure, 159 +/- 4/103 +/- 4 mmHg; mean +/- SEM) were studied. We measured forearm blood flow by a strain gauge plethysmograph while infusing phenylephrine (1, 4, 12 nmol/min) and angiotensin II (5, 10, 20 pmol/min) locally into the brachial artery before and during simultaneous intra-arterial infusion of human insulin (0.15 mU/kg/min). Forearm vascular resistance was calculated from directly measured arterial pressure and forearm blood flow. Intra-arterial infusion of insulin raised the local plasma insulin level without changing the blood glucose level, basal forearm blood flow, or forearm vascular resistance. Phenylephrine and angiotensin II increased forearm vascular resistance dose-dependently before and during insulin infusion. In contrast to the previous results in normotensive subjects, locally infused insulin did not attenuate vasoconstrictive responses to phenylephrine and angiotensin II in patients with essential hypertension. These results suggest that the balance between the pressor and depressor effects of insulin might be altered in favor of a pressor effect in patients with hypertension.
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PMID:Effects of intra-arterial infusion of insulin on forearm vasoreactivity in hypertensive humans. 758 33

The involvement of adenosine 3',5'-cyclic monophosphate (cAMP) in the stimulation of ventricular protein synthesis by aortic hypertension or adrenergic agonists in the adult rat heart was investigated. In either the retrogradely or anterogradely perfused heart, aortic hypertension increased protein synthesis rates by up to 19%. However, no changes in cAMP concentrations or in cAMP-dependent protein kinase activity ratios could be detected either at early (< 5 min) or late (90 min) time points. Although isoproterenol, 3-isobutyl-1-methylxanthine, or forskolin raised cAMP concentrations (by up to 4.5-fold) and cAMP-dependent protein kinase ratios (by up to 4-fold), protein synthesis rates were not increased; however, under some perfusion conditions, glucagon did stimulate protein synthesis by 25%. Epinephrine stimulated protein synthesis by up to 32%, an effect that was not prevented by propranolol. Phenylephrine also stimulated protein synthesis, an effect that was prevented by prazosin but was unaffected by yohimbine. These findings implicate the alpha 1-adrenoceptor in the regulation of cardiac protein synthesis. Because changes in adenine nucleotide concentrations were similar in hearts perfused with epinephrine or with the agents that raised cAMP, it is unlikely that adenine nucleotide depletion is responsible for the failure to observe effects of the latter group of agents on protein synthesis. Although isoproterenol or forskolin raised cAMP concentrations in isolated ventricular cardiomyocytes where ATP depletion was minimal, neither stimulated protein synthesis. alpha 1-Adrenergic agonists stimulate phosphoinositide hydrolysis in the heart (Brown, J. H., I. L. Buxton, and L. L. Brunton. Circ. Res. 57:532-537, 1985). Aortic hypertension doubled the rate of phosphoinositide hydrolysis in the perfused heart. We suggest that the phosphoinositide-linked signal transduction pathway is more likely to be involved in stimulation of cardiac protein synthesis by hypertension or adrenergic agonism than the adenylyl cyclase/cAMP-linked pathway.
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PMID:cAMP and protein synthesis in isolated adult rat heart preparations. 769 91

In 3 dogs scheduled for surgical removal of cataracts, systemic and topical treatment with antibiotics and topical ocular treatment with prednisolone, atropine, flurbiprofen, and phenylephrine were used to achieve maximal mydriasis, with minimal risk of pupillary constriction in response to surgery. Each dog developed arterial hypertension, with systolic, diastolic, and mean arterial pressures ranging from 170 to 205, 90 to 112, and 123 to 148 mm of Hg, respectively. Hypertension was treated with acepromazine maleate (0.001 to 0.005 mg/kg of body weight) i.v., decreasing arterial pressures to reference values. Phenylephrine dosages for topical use ranged from 50 to 367 times greater than the i.v. dose required to increase arterial pressure by 50% in anesthetized dogs. Although adverse sequelae to these episodes of hypertension were not noticed, this report documents the uptake of phenylephrine from topical ocular application and suggests the need for dose-response measurements for this adjunct to mydriatic treatment in dogs.
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PMID:Arterial hypertension associated with topical ocular use of phenylephrine in dogs. 776 84

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter and/or neuromodulator in the central nervous system [Misu Y. and Goshima Y. (1993) Trends pharmac. Sci. 14, 119-123]. This study aimed to explore whether or not endogenous L-DOPA, as a neurotransmitter candidate of the primary baroreceptor afferents, tonically functions to activate depressor neurons in the nucleus tractus solitarii of anesthetized rats. By parallel microdialysis in bilateral nucleus tractus solitarii areas, the basal L-DOPA release was in part inhibited by tetrodotoxin perfusion (1 microM) or Ca2+ deprivation, and was markedly reduced by alpha-methyl-p-tyrosine (200 mg/kg, i.p.), a tyrosine hydroxylase inhibitor. Forty to 100 mM K+ concentration-dependently released L-DOPA. Fifty millimoles K+ repetitively and constantly released L-DOPA. This release was Ca(2+)-dependent. Stimulation of the left aortic nerve (100 Hz, 8 V) repetitively and constantly released L-DOPA and this release was tetrodotoxin-sensitive. Phenylephrine i.v. infused produced L-DOPA release and reflex bradycardia, temporally associated with a rise and subsequent recovery of blood pressure. This release and bradycardia were abolished by denervation of the bilateral carotid sinus and aortic nerves. In addition, L-DOPA methyl ester, a competitive L-DOPA antagonist, when microinjected into depressor sites of the left nucleus tractus solitarii, antagonized depressor responses to mild stimulation (20 Hz, 3 V) of the ipsilateral aortic nerve. This antagonist alone, microinjected bilaterally, elicited a dose-dependent hypertension, which was abolished by alpha-methyl-p-tyrosine. Furthermore, by immunocytochemical analysis seven days after denervation of the left aortic nerve, tyrosine hydroxylase- and L-DOPA-, but not dopamine- and dopamine-beta-hydroxylase-immunoreactivities decreased in the ipsilateral nucleus tractus solitarii and dorsal motor vagus nucleus complex area. In the left ganglion nodosum, denervation decreased staining and number of L-DOPA-immunoreactive cells and staining of tyrosine hydroxylase-immunoreactive cells, but no modification of dopamine-immunoreactive cells was seen. Taken together with previous findings that L-DOPA itself is stereoselectively responsible for cardiovascular control in this nucleus, it is probable that L-DOPA is a neurotransmitter of the primary baroreceptor afferents terminating directly in depressor neurons and/or indirectly in some neurons within a microcircuit, including depressor neurons of the nucleus tractus solitarii. Endogenously released L-DOPA itself tonically functions to activate depressor neurons for regulation of blood pressure in the rat nucleus tractus solitarii.
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PMID:Baroreceptor-aortic nerve-mediated release of endogenous L-3,4-dihydroxyphenylalanine and its tonic depressor function in the nucleus tractus solitarii of rats. 781 96

Brainstem catecholaminergic neurons have been implicated as mediating adaptive autonomic and neuroendocrine responses to cardiovascular challenges. To clarify the nature of this involvement, immuno- and hybridization histochemical methods were used to follow c-fos expression in these neurons in response to acute stimuli that differentially affect blood pressure and volume. From low basal levels, hypotensive hemorrhage (15%) provoked a progressive increase in the number and distribution of Fos-immunoreactive (ir) nuclei in the nucleus of the solitary tract (NTS), the A1 and C1 cell groups of the ventrolateral medulla, and in the pontine A5, locus coeruleus, and lateral parabrachial cell groups peaking at 2.0-2.5 hours after the challenge. Fos-ir ventrolateral medullary neurons, subsets of which were identified as projecting to the paraventricular hypothalamic nucleus or spinal cord, were predominantly aminergic, whereas most of those in the NTS were not. Infusion of an angiotensin II antagonist blunted hemorrhage-induced Fos expression in the area postrema, and attenuated that seen elsewhere in the medulla and pons. Nitroprusside-induced isovolemic hypotension yielded a pattern of c-fos induction similar to that seen following hemorrhage, except in the area postrema and the A1 cell group, where the response was muted or lacking. Phenylephrine-induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to non-aminergic neurons, whose distribution in the NTS conformed to the termination patterns of primary baroreceptor afferents, and in the ventrolateral medulla overlapped in part with those of vagal cardiomotor and depressor neurons. These findings underscore the importance of brainstem catecholaminergic neurons in effecting integrated homeostatic responses to cardiovascular challenges and their ability to responding strategically to specific modalities of cardiovascular information. They also foster testable predictions as to effector neuron populations that might be recruited to respond to perturbations in individual circulatory parameters.
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PMID:Spatially and temporally differentiated patterns of c-fos expression in brainstem catecholaminergic cell groups induced by cardiovascular challenges in the rat. 784 57

While growth of blood vessels is important in hypertension, relatively little is known about the contribution of catecholamines. Using isolated rat aorta and cultured smooth muscle cells, we examined adrenergic stimulation of gene expression. Phenylephrine, a selective alpha 1 adrenergic receptor agonist, caused a rapid and transient increase in c-fos mRNA accumulation which was inhibited by prazosin, an alpha 1 receptor antagonist. Similarly, phenylephrine stimulated c-jun and c-myc mRNA accumulation. Chloroethyl-clonidine, a compound which irreversibly blocks alpha 1B receptors, completely blocked the phenylephrine-induced increase in c-fos mRNA. RNase protection experiments demonstrated that rat aorta prominently expressed mRNA for alpha 1B and alpha 1A/D receptors. Phenylephrine-induced c-fos mRNA was partially inhibited by H-7, a protein kinase C inhibitor, and by nifedipine, a Ca2+ channel blocker; these two compounds together had additive effects. In situ hybridization showed that expression of c-fos mRNA induced by phenylephrine was localized to aorta's medial layer. These results suggest that alpha 1 receptor-induced increase in c-fos mRNA in aorta is mediated by a chloroethyl-clonidine-sensitive receptor subtype signaling via increasing intracellular Ca2+ concentrations and activating protein kinase C.
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PMID:Alpha 1 adrenergic receptor-induced c-fos gene expression in rat aorta and cultured vascular smooth muscle cells. 804 Feb 63


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