Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guancydine (1-cyano-3-tert-amylguanidine) lowered within normal limits the tensional values in an interval of four hours after its administration in eight out of nine hypertensive patients under experiment. The hypotensive effect of a single oral dose of 500-750 mg persists for about 6-7 hours after its administration. Guancydine does not impair the vasopressor response to angiotensin II but reduces the action of this peptide on the excretion of water, Na, K and Ca through urine. The hypotensive effect of Guancydine is associated with a decrease of platelet adhesiveness and an activation of fibrinolysis. In view of this fact, Guancydine might play a role in the prophylaxis of complications of arterial hypertension - atherosclerosis and trombosis. The increase of venous blood oxygenation after Guancydine could be attributed to the opening of arterio-venous shunts or to the reduction of tissular extraction of oxygen. Guancydine does not seem to be toxic. It produced, in some patients, slight headache and orthostatic hypotension, especially during the first hours after administration.
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PMID:Guancydine, a new hypotensive agent with complex action. 56 30

Endothelial cells are not just a semipermeable membrane that forms a barrier between the blood and the vascular smooth muscles. This cell system is a highly active metabolic endocrine organ. It not only produces a number of important substances in vascular and neural homeostasis but also inactivates vasoactive substances such as serotonin and bradykinin. In addition, it produces endothelin-1 and angiotensin II; more importantly in the context of migraine, endothelial cells produce the vasodilators prostacyclin and EDRF-NO, both of which are local (paracrine) hormones. The physiologic function of endothelial cells is affected by aspirin, which prevents prostacyclin formation but has little effect on normal blood pressure. From this information, one can infer that endothelial cell production of prostacyclin does not play an important part in normal cardiovascular control. On the other hand, the administration of Ng-monomethyl-L-arginine causes immediate increases in blood pressure. Because the administration of this substance inhibits the release of EDRF-NO, it appears that this paracrine endothelial hormone actively dilates the normal circulation. It is of cardinal importance that damage or flow perturbations of cell membranes of the endothelial lining of blood vessels cause an increased production of prostaglandins. However, smooth muscle cells underlying the endothelial lining also synthesize prostacyclin. This mechanism is thought to be held in reserve to reinforce local production of prostacyclin and vasodilatation when cell damage to the endothelial lining occurs and EDRF-No is not produced. Many theories for the causation of migraine have been proposed, and some have been reviewed. Those holding sway tend to ignore inconsistencies and cite supporting evidence in favor of their pet explanation only. I therefore have no hesitation to show that the best explanation at present, based on the most recent cellular evidence, explains all features of migraine and the response of migraineurs to therapy. The endothelial cell is the most likely site of the primary abnormality (Fig. 1). Although under physiologic circumstances perivascular innervation and endothelial systems closely interact in the control of vascular tone during pathologic conditions such as ischemia, the dominant role in protecting the circulation is endothelium-mediated. The biology of headache is so diverse and our ignorance sufficiently pervasive that the investigation of endothelial cell function may solve the mystery of migraine. To match the postulated crucial role of the endothelial cell in the pathogenesis of migraine, another cell would have to be ubiquitously present throughout the vasculature and not just confined to the central nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of migraine. 202 Feb 28

Recently there has been extensive development of orally active angiotensin converting enzyme (ACE) inhibitors in addition to those already marketed, for example, captopril, enalapril, lisinopril and ramipril. It was initially thought that ACE inhibitors were likely to be most useful as antihypertensive agents in conditions in which circulating renin and angiotensin II were elevated. However, it is now clear that they can also lower arterial pressure when plasma renin is not high. In addition, they have beneficial effects in cardiac failure. Thus, captopril, enalapril, lisinopril and ramipril can be used in the treatment of mild to moderate hypertension either alone or in conjunction with diuretics or calcium antagonists. Broadly speaking, efficacy appears to be similar to that of beta-blockers or diuretics. Unfortunately, however, there are no long term studies comparing one ACE inhibitor with another or with other classes of antihypertensive agents. Furthermore, there are no prognostic studies which show that use of ACE inhibitors reduces morbidity or mortality in hypertension. Many new ACE inhibitors are undergoing clinical assessment, including alacepril, cilazapril, fosenopril, perindopril, quinapril and ramipril. The drugs vary, in that some exist in the active form whereas others are prodrugs which are converted to the active agent following absorption. In addition they each possess one of several ligands, for example, carboxyl, phosphinyl or sulfhydryl groups, and so vary in their affinity for ACE. Although many of these agents are renally excreted, a small number are metabolised via the liver (e.g. quinapril and spirapril) and this may prove advantageous in the presence of renal impairment. In common with captopril and enalapril, the new ACE inhibitors inhibit the renin-angiotensin system and initial results suggest that they are effective in lowering blood pressure in essential hypertension. Furthermore, they reduce systemic vascular resistance in the absence of a reflex tachycardia. There are a number of adverse effects which are attributable to the pharmacological mechanism of the ACE inhibitors as a group; these include hypotension, particularly in patients with high renin levels, prior diuretic use, renal impairment or in the elderly. Additional adverse effects may relate to chemical structure. The high incidence of adverse effects noted in early studies related to excess dosage and to the presence of a sulfhydryl group, which the more recently developed ACE inhibitors lack. The adverse effects most commonly reported with established and new ACE inhibitors include headache and fatigue, cough, skin rashes, hypotension and diarrhoea. As a group, ACE inhibitors have an acceptable but not negligible adverse effect burden.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin converting enzyme inhibitors and moderate hypertension. 222 19

Twenty patients with bladder cancer were treated with intra-arterial infusion chemotherapy using CDDP and ADM in combination with [Sar1, Ile8] angiotensin II. A catheter was introduced into internal iliac artery by Seldinger's technique, and 100 mg of CDDP, 50 mg of ADM and 1 mg of [Sar1, Ile8] angiotensin II were infused through the catheter for 40 minutes. CR was observed in 8 of 20 patients. PR in 11 and NC in 1. Therefore, the response rate (CR + PR) was 95% (19/20). Side effects were generally mild and consisted of leukopenia, nausea, vomiting, diarrhea, alopecia, skin pigmentation and headache. Catheter-related complications were not observed. This study demonstrated that intra-arterial infusion chemotherapy with CDDP and ADM in combination with [Sar1, Ile8] angiotensin II was extremely effective in treating patients with bladder cancer.
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PMID:[Intra-arterial infusion chemotherapy with [Sar1, Ile8] angiotensin II in bladder cancer]. 280 36

Enalapril maleate is a new angiotensin converting enzyme inhibitor marketed in the U.S. by Merck Sharp and Dohme. It has been demonstrated to actively interfere with the renin-angiotensin-aldosterone system. This is reflected by both hemodynamic (decreased blood pressure) and humoral (increased plasma renin, angiotensin I, and decreased angiotensin II) responses to enalapril therapy. Activity in the kallikrein-bradykinin system is still controversial. Enalapril maleate is a prodrug which is quickly absorbed, hydrolyzed by the liver to the active metabolite enalaprilic acid, and excreted 33 percent in the bile and 61 percent in the urine. The therapeutic dosage range is 10-40 mg/d, maximum of 40 mg, given once or twice daily. The onset and duration of action are dose related. Vertigo and headache have been the most commonly reported side effects. Clinical comparison of enalapril to hydrochlorothiazide, beta-adrenergic blockers, and captopril find it efficacious in the treatment of essential hypertension. Efficacy in treating congestive heart failure and hypertension secondary to renal artery stenosis has also been demonstrated for both angiotensin converting enzyme inhibitors. The overall efficacy and safety of enalapril and captopril appear equivalent when used at low doses in patients with uncomplicated hypertension.
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PMID:Enalapril: a new angiotensin converting enzyme inhibitor. 300 62

Experiments were performed to assess the ability of bencianol (ZY15051) to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the aetiology of migraine and cerebral arterial spasm. Bencianol caused a dose-related (1-100 micrograms ml-1) reversal of contractions induced by 5-hydroxytryptamine, noradrenaline, angiotensin II, prostaglandin F2 alpha, and U-46619 (a thromboxane-A2 mimetic). Bencianol was more effective against contractions induced by EC50 compared to maximal concentrations of each agent, and was least effective against the thromboxane-A2 mimetic, U-46619. In addition, contractions induced by thromboxane-A2-like substances generated from guinea-pig lungs were also reversed by bencianol but only at the highest concentration used (100 micrograms ml-1). The relevance of this action of bencianol to migraine and cerebral arterial spasm is discussed.
Cephalalgia 1985 Dec
PMID:Anti-spasmogenic effects of bencianol (ZY15051) on human cerebral arteries in vitro. 408 77

A 34-year-old female complaining of numbness and weakness of the extremities was examined. Consanguineous marriage was contracted between mother and father. She was of short stature (149 cm), and her blood pressure was normal (118/60 mmHg). Her serum potassium concentration had decreased to a level between 2.5 and 3.2 mEq/L, and hypokalemic alkalosis was present. Potassium clearance had increased and urinary concentrating capacity was impaired. Plasma renin activity was high at 25 ng/ml/hr but plasma aldosterone concentration was normal. Hypertensive response to angiotensin II (50 ng/kg/min) was weak but improved to nearly the normal value after the administration of indomethacin for 17 days at a dose of 50 mg/day. A slight elevation in blood pressure was observed during the infusion of norepinephrine (250 ng/kg/min). A decrease in blood pressure was observed during the infusion of 1-sarcosine, 8-isoleucine angiotensin II (600 ng/kg/min) with concomitant increase of plasma renin activity. Twenty-four hour urinary excretion of prostaglandin E decreased somewhat (225 approximately 252 ng/day), and hyperplasia of the juxtaglomerular cells and increased JG index were demonstrated in the biopsy specimens of the right kidney. From the findings, the present case were diagnosed as Bartter's syndrome. Although mild enlargement of the sella turcica was found in skull x-ray films, no abnormalities in pituitary function were demonstrated. Other unusual complications, i.e. hyperlipidemia (type II, beta-dominant) and abnormal configuration of peripheral erythrocytes, were demonstrated. Phospholipid composition of the erythrocyte membrane was normal. The fluidity of plasma VLDL examined by electron spin resonance was increased. Hypokalemia and hyperreninemia were improved through the administration of indomethacin. However, because of headache as an adverse effect, further administration could not be accepted. The patient's complaints were resolved by the rectal application of indomethacin with oral administrations of spironolactone and triamterene. Changes in serum lipid levels did not occur with the above mentioned treatment. alpha-tocopheryl nicotinate lowered the levels of serum lipids and normalized the configuration of peripheral erythrocytes. But increased fluidity of plasma VLDL remained, and phospholipid composition of erythrocyte membrane was also unchanged. The relationship between the rare complications mentioned above and the pathophysiology of Bartter's syndrome is still obscure.
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PMID:[A case with Bartter's syndrome associated with type II hyperlipidemia, increased fluidity of plasma VLDL and abnormal configuration of peripheral erythrocytes (author's transl)]. 704 42

This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered "drug-related" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.
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PMID:Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. 771 81

In angiotensin II (A II)-induced hypertension chemotherapy (IHC), the role of the level of hypertension induced by A II and pattern of maintenance of the state was investigated in 5,840 IHC records of 264 patients. The pattern of IHC records of each patient was evaluated according to the range of the mean elevated blood pressure (MBPe) and induced hypertension point (IHTP). The MBPe of each record was calculated from 5-7 randomly selected values. The range of MBPe from each record was estimated, while discarding the max and min values. IHTP was classified into three categories as follows: 1:160 > MBPe > or = 140, 2: MBPe > 160 and 140 > MBPe > or = 130; and 3: 130 > MBPe. The most frequent category of all records was determined as the IHTP of each patient. One point was added to IHTP, when the fluctuation range of MBPe was more than 10 mmHg, and when the other categories were mixed more than 25% among all records. The MBPe of CR + PR group were significantly higher than in the other non-response group. IHTP was also better in responders. Many patients aged below 40 responded poorly to A II, and the level of MBPe was significantly lower than that of patients above 40. It may be essential to induce the hypertensive level and maintain a stable state during IHC for enhancement of clinical effects. Symptoms accompanied during IHC such as chest oppressive sense, dull head pain, and abdominal discomfort were observed in half the patients, although the IHC procedure almost never had to be discontinued.
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PMID:[Smooth induction and stable maintenance of hypertensive state for clinical response in angiotensin II-induced hypertension chemotherapy]. 788 38

Valsartan competitively and selectively inhibits the actions of angiotensin II at the AT1 receptor subtype which is responsible for most of the known effects of angiotensin II. In clinical trials in patients with mild to moderate essential hypertension valsartan was as effective as losartan, lisinopril, enalapril, amlodipine and hydrochlorothiazide. Addition of the latter reduced blood pressure in patients who did not respond sufficiently to valsartan monotherapy. Preliminary data also suggest valsartan may be effective in patients with severe essential hypertension. The drug was as effective as lisinopril as treatment for mild to moderate essential hypertension in patients with renal insufficiency and did not worsen renal function. Headache, dizziness and fatigue were the most common adverse events in placebo-controlled studies; the incidence of these adverse events was not significantly different between placebo and valsartan recipients. Compared with ACE inhibitors, valsartan was associated with a significantly lower incidence of dry cough. Thus, valsartan is an effective treatment for mild to moderate essential hypertension and may be particularly useful in patients who experience persistent cough during ACE inhibitor therapy.
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PMID:Valsartan. A review of its pharmacology and therapeutic use in essential hypertension. 925 84


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