Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed Fourier analysis of the middle cerebral artery blood flow velocity waveform envelope in 14 normal subjects (group A) and 15 patients, of whom five had arteriovenous malformations (group B), five had cerebral vasospasm (group C), and five had arterial hypertension (group D). Measurements were obtained under conditions of normocapnia, hypercapnia, and hypocapnia. The Fourier coefficients measured in the first five harmonics of the Doppler waveforms of group A were used as the reference baseline and were compared with the coefficients found in the other three groups. Group B showed significantly lower Fourier coefficients, while groups C and D showed higher coefficients (p less than 0.05). The elevation of the Fourier coefficients occurred in an alternating pattern in group C and a decremental pattern in group D. This distinction was attributed to possible differences in the underlying pathophysiological processes. The degree of vascular distensibility of the cerebral arterioles, inferred from the shape of the Fourier analysis curves, was compared in all four groups. Vascular distensibility was characterized as abnormal in arteriovenous malformations, vasospasm, and arterial hypertension. Fourier coefficients may be better indicators of cerebrovascular abnormalities than mean blood flow velocity in hypertension and pulsatility index in arteriovenous malformations, vasospasm, and hypertension.
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PMID:Fourier analysis of the cerebrovascular system. 205 69

It is suggested that endothelin-1 (ET-1), a potent vasoconstrictor peptide, is involved in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). We examined the effects of intracisternal administration of big ET-1 on the cerebral arteries in the absence or presence of pretreatment with phosphoramidon, an inhibitor of ET converting enzyme, in anesthetized dogs. After intracisternal administration of big ET-1 (10 micrograms/dog), the caliber of the basilar artery on the angiogram was decreased to about 59% of the control. This was accompanied by a marked increase in immunoreactive ET in the cerebrospinal fluid. Systemic arterial pressure was markedly elevated following big ET-1 injection. All changes induced by big ET-1 were effectively prevented with phosphoramidon. These data suggest that intracisternally administered big ET-1 is converted to ET-1 and that the generated ET-1 produces cerebral vasospasm and hypertension. A phosphoramidon-sensitive metalloproteinase appears to contribute to this conversion.
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PMID:Phosphoramidon inhibits the conversion of intracisternally administered big endothelin-1 to endothelin-1. 206 64

In summary, over a period of approximately four decades, an important new pathologic process was identified. There is no longer any doubt that the deposition of the subarachnoid clot in the basal cisterns can, over the course of a few days, lead to a progressive, severe vasoconstriction. This, in turn, can reduce cerebral blood flow to the distal brain, which, depending on a multitude of factors, can result in cerebral infarction. It is highly likely that the erythrocyte is the most important blood element in the pathophysiology of this process. The exact mechanism by which the blood vessel is forced into this destructive spasm remains to be elucidated. Significant steps have been taken to avoid the consequences of vasospasm by using hypertension and hypervolemia (or at the very least avoiding iatrogenic hypotension and hypovolemia). These measures have resulted in a reduced incidence of delayed ischemia. Because clot has been shown to cause vasospasm, it has seemed only logical that the early removal of clot would be efficacious in its prophylaxis. Experimental and clinical evidence to support this view has been gathered. Therapeutic measures based on it have been shown to be effective in the experimental situation but await controlled clinical evaluation. In the past decade, thanks to such trials, one of the calcium antagonist drugs has been shown to be effective in improving the outcome following subarachnoid hemorrhage, probably on the basis of reducing the frequency and extent of infarction by small vessel dilatation or neuronal protection. Although patients still die from this lethal complication of subarachnoid hemorrhage, it is difficult not to have some measure of optimism, based on the history just reviewed, that cerebral vasospasm will be a treatable disease within a few decades.
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PMID:The history of cerebral vasospasm. 213 40

This review of the clinical studies of thromboxane synthase inhibitors (TXSIs) and thromboxane receptor blocking drugs (TXRBs) covers the years 1981 to the present. Clinical studies on TXSIs include those in normal volunteers as well as those in patients with angina, peripheral vascular disease and Raynaud's syndrome, pulmonary hypertension, cerebral vasospasm, hepatorenal syndrome, adult respiratory distress syndrome, and those on cardiopulmonary bypass and hemodialysis. The compounds studied include dazoxiben, dazmagrel, CGS 13080, CV 4151, OKY 1581, OKY 046, and U 63557A. In volunteers, single-dose studies have demonstrated inhibition of thromboxane A2 (TXA2) formation, with some small increases in bleeding time but no marked effect on platelet aggregation. In general, the compounds tested were ineffective in both chronic stable angina and vasospastic angina but caused symptomatic improvement in patients with unstable angina. The TXSIs studied were found to produce no consistent effects in any of the other clinical conditions. Since none of the compounds tested produced a sustained inhibition of TXA2 synthesis, the disappointing clinical results with this class of drugs may be due to an incomplete blockade of thromboxane synthase with the dosage regimens used. Possible alternative or additional reasons for the general lack of success with TXSIs could be that some of the diseases studied do not involve TXA2 or that accumulating prostaglandin endoperoxides in the presence of thromboxane synthase inhibition substitute for TXA2 in causing platelet aggregation. TXRBs rely for their efficacy only on blockade of the TXA2 receptor and antagonize the deleterious effects of both TXA2 and prostaglandin H2 equally, so they represent a simpler pharmacological approach than TXSIs. Such drugs include AH 23848, GR 32191, BM 13.177, BM 13.505, and SQ 28668. All of these compounds are inhibitors of platelet aggregation induced by TXA2 or by its stable mimetic, U-46619. AH 23848 was ineffective in patients with stable angina but did benefit patients with peripheral vascular disease. BM 13.177 has also proven effective in preventing restenosis after angioplasty, occlusion of coronary artery bypass grafts, and the deleterious effects of TXA2 in renal disease. From these preliminary studies, it would appear that TXRBs may offer greater clinical potential than TXSIs. Further studies currently underway with TXRBs to resolve this question include those in unstable angina, angioplasty, peripheral vascular disease, renovascular hypertension, and cyclosporine nephrotoxicity.
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PMID:Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review. 213 20

1. Endothelial cells of blood vessels generate factors which can modulate underlying smooth muscle tone, inducing vasorelaxation, (endothelium-derived relaxing factor, EDRF, and endothelium-derived hyperpolarizing factor) and/or vasoconstriction (endothelium-derived contracting factors, EDCFs, including the peptide endothelin). 2. EDRF is nitric oxide (NO) or a RNO compound from which this oxide is released. Its half-life is very short (6-50 sec), and it produces rapid vasodilations and inhibits platelet aggregation. 3. NO is formed from the terminal guanidino of L-arginine, but not of D-arginine. NO effects and NO formation are inhibited by NG-monomethyl-L-arginine (L-NMMA), but not by D-NMMA. These inhibitory effects are blocked by L-arginine. 4. Removal of endothelium or pathological situations that can induce endothelial dysfunction (atherosclerosis, diabetes, hypertension or subarachnoid hemorrhage) cause increases on the vascular contractility elicited by agonists (noradrenaline, serotonin, EDCFs, etc.). These findings suggest that EDRF produces a physiological inhibitory modulation of vascular smooth muscle tone and its alteration produces or facilitates the development of diseases such as hypertension or coronary and cerebral vasospasm.
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PMID:Role of endothelium-formed nitric oxide on vascular responses. 227 79

1. Vascular endothelium releases different substances (endothelium-derived contractile factors, EDCFs), which mediate vasoconstrictor responses induced by several agents. 2. Clear differences have been reported in endothelium-dependent contractions, which suggest at least three distinct EDCFs, named EDCF1, EDCF2 and EDCF3, respectively. 3. EDCF1 is a cyclooxygenase metabolite(s) of arachidonic acid. EDCF2 is a polypeptide released from cultured endothelial cells. It has been isolated and identified as a 21-amino acid peptide called endothelin, which is described as the most potent vasoconstrictor agent known to date. EDCF3 is an unidentified contractile factor(s), which is neither EDCF1 nor EDCF2. 4. The physiological role of these endothelial contractile factors is not yet clear. However, they have been implicated in the local mechanisms involved in blood flow regulation, as well as in some pathological conditions, such as hypertension or cerebral vasospasm.
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PMID:Endothelium-derived contractile factors. 227 80

We showed that normovolaemic induced hypertension therapy was effective in reducing ischaemic symptoms attributed to cerebral vasospasm in 41 patients after subarachnoid haemorrhage. By inducing hypertension to 25% to 50% above normal systolic arterial blood pressure, we observed that in 17 of 24 cases (71%) neurological deficits improved. In four cases of haemorrhagic infarction, the blood pressure rose to over 50% of systolic arterial pressure, and a low density area was confirmed on computerized tomography (CT) scan prior to vasospasm. Induced hypertension was therefore not considered when a low density area was revealed on CT scan. Restriction of fluid input is usually a factor in producing hypovolaemia after a neurosurgical operation. Intravascular volume expansion has been reported effective in reversing ischaemic deficits. However, according to Poiseuille's equation, increasing blood volume to a state of hypervolaemia can not enhance flow. The cerebral blood flow (CBF) was raised by increasing perfusion pressure, reducing viscosity, or increasing blood vessel diameter. Intravascular volume expansion elevates not only systemic arterial pressure, but also pulmonary artery wedge pressure over 18 mmHg and cardiac index over 2.2. Since pulmonary oedema and congestive heart failure may develop, one should monitor haemodynamic parameters with the Swan-Ganz catheter as a preventive measure. We emphasize that normovolaemic induced hypertension, maintaining haemodynamics subset 1 of the comparable haemodynamic subsets, is effective in raising perfusion pressure of CBF.
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PMID:Normovolaemic induced hypertension therapy for cerebral vasospasm after subarachnoid haemorrhage. 236 Apr 62

Treatment with the calcium entry blocker nimodipine is recommended as effective therapy for cerebral ischemia due to cerebral vasospasm or cerebral thrombosis. On the other hand, treatment with induced hypertension is a widely accepted measure to reverse ischemic deficits caused by vasospasm. Thus, a combination of the two regimens--nimodipine and induced hypertension--may have real benefits for cerebral ischemia. But it is possible that the benefit of one is abolished by adverse effects of the other, or that a combination of both may not be as effective as the use of only one therapy. In order to investigate these problems, the effects of nimodipine and induced hypertension on cerebral vessel, cerebral blood flow, cerebral edema and cerebral infarction using a one hour middle-cerebral-artery occlusion model in cats. Twenty-one anesthetized cats were divided into a control group, the nimodipine-treated group, and the nimodipine-and-induced-hypertension group. There were seven cats in each group. Occlusion of the middle cerebral artery (MCA) was continued for one hour in each animal. Induced hypertension was a little higher than resting values, and it was continued for only one hour during MCA occlusion, brought on by instillation of dopamine. Cerebral pial arteries dilated much more prominently during and after the occlusion of MCA in the nimodipine-and-induced-hypertension group than other groups. Although cerebral blood flow in the nimodipine group, and the nimodipine-and-induced-hypertension group increased more in the non-ischemic hemisphere, the most remarkable increase was seen around the infarcted cortex in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of calcium antagonist nimodipine and induced hypertension on cerebral vessel reactivities, cerebral blood flow, cerebral edema and infarction in cats with one hour middle-cerebral-artery occlusion]. 238 17

The pathophysiology and treatment of acute subarachnoid hemorrhage (SAH) are reviewed. SAH occurs when blood is released into the subarachnoid space, which surrounds the brain and spinal cord. Symptoms of SAH include severe headache, nausea, vomiting, neck pain, nuchal rigidity, and photophobia. The initial hemorrhage is fatal in 20-30% of patients. Complications of SAH include rebleeding, hydrocephalus, delayed cerebral ischemia associated with cerebral vasospasm, and seizures. The likelihood of rebleeding is increased by measures that rapidly lower intracranial pressure. The risk of developing hydrocephalus is associated with the volume of blood within the subarachnoid space and ventricular system. Cerebral vasospasm develops in 20-40% of patients, and up to 50% of affected patients die or suffer permanent neurological damage. Seizures occur in 5-15% of patients with SAH. Radiologic procedures form the foundation for the diagnosis of SAH. The most commonly used rating scale classifies the severity of SAH based on the clinical presentation of the patient. Surgery is the definitive treatment for the prevention of rebleeding. Hydrocephalus can only be treated surgically, most commonly by insertion of a drain. The only measures proved to be effective for treatment of delayed cerebral ischemia are volume expansion and the induction of hypertension. The calcium-channel blocker nimodipine was recently approved for treatment of arterial spasm in SAH. Intravenous nicardipine is also being studied for the same indication. These agents may improve clinical outcome substantially by limiting fixed neurological deficits. To prevent seizures, prophylactic antiepileptic therapy with phenytoin sodium is generally accepted. The SAH complications of rebleeding, hydrocephalus, delayed cerebral ischemia, and seizures are managed by surgical, drug, and fluid therapy.
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PMID:Pathophysiology and treatment of subarachnoid hemorrhage. 240 1

The mechanism of action of calcium channel modulators, a class of drugs that includes 3 chemical groups--1,4-dihydropyridines, phenylalkylamines and benzothiazepines--has been extensively reviewed. The best known representatives of these 3 groups are nifedipine, verapamil and diltiazem, respectively. These drugs bind reversibly, stereospecifically and with high affinity to both the membrane-bound and the purified receptor complex. Non-dihydropyridines allosterically regulate dihydropyridine binding. This has been shown by using (-) [3H]202-791 and (+) [3H]PN200-110 as labeled ligands. The purified receptor complex that possesses binding sites for all 3 chemical groups is likely to be related to the voltage-dependent calcium channel. As the result of a drug-receptor interaction, voltage-dependent calcium channels are either activated or inactivated. The drugs that activate channels act by promoting long-lasting channel openings. The drugs that inhibit calcium channels, the calcium entry-blocking agents, act by preventing channel openings upon membrane depolarization. A complex pharmacologic, electrophysiologic, biochemical, immunologic and molecular genetic approach is required to determine the molecular mechanism of action of calcium channel modulators. Clinically, calcium entry-blocking agents are recommended for the treatment of angina pectoris, hypertension, posthemorrhagic cerebral vasospasm, supraventricular tachycardia, migraine and asthma and the protection of the ischemic myocardium.
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PMID:Receptor pharmacology of calcium entry blocking agents. 243 27


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