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

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.
 ...
PMID:The future of calcium channel blocker therapy in diabetes mellitus. 172 50

Endothelial cells can produce contracting factors; endothelin, a 21-amino acid peptide that can control local vascular tone, is the most potent of these factors. Of the three isoforms of endothelin, endothelial cells appear to release primarily endothelin-1. The peptide is formed from its precursor big endothelin via the activity of the endothelin converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and the calcium ionophore A23187. In vascular smooth muscle cells, endothelin binds to a specific receptor that activates phospholipase C and leads to the formation of inositol trisphosphate, diacylglycerol, and increased intracellular calcium levels. In certain blood vessels, the endothelin receptor is linked to a voltage-operated calcium channel via a Gi protein. This may explain why calcium antagonists inhibit endothelin-induced contractions only in certain blood vessels. In the human forearm circulation, calcium antagonists of different classes prevent endothelin-induced contractions. In hypertension, the circulating endothelin levels appear to be normal, whereas the vascular sensitivity to the peptide is reduced in most vascular tissues, but normal and enhanced responses have also been reported. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are augmented, a phenomenon that may be related to an increased formation of the peptide induced by modified forms of low-density lipoproteins.
 ...
PMID:Endothelin. 172 99

Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean +/- SE) 74 +/- 2 vs 60 +/- 4 mg/dl (P less than 0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 +/- 2 vs 37 +/- 3 mg/dl, P less than 0.005). Notably plasma triglycerides (TG) and low density lipoprotein-cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P less than 0.05) and 3 hr (P less than 0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2% intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P less than 0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2% intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27%), TG transport (31%) and chylomicron-TG output (37%), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA-3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.
 ...
PMID:The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents. 172 31

Acute postoperative hypertension (APH) has been documented in the PACU. Over half of the patients who exhibit APH have pre-existing primary hypertension. Sustained blood pressure (BP) elevation increases the risk of myocardial ischemia, infarction, surgical site bleeding, or cerebral hemorrhage in these patients. Following surgery and anesthesia, increased sympathetic stimulation caused by a high level of circulating catecholamines can lead to APH. Some direct perioperative stimulants include pain, anxiety, hypoxia, hypercapnia, hypothermia, shivering, volume overload, and bladder distension. Nursing interventions are directed toward identifying and relieving the cause of APH. Antihypertensive drug therapy with vasodilators or adrenergic inhibitors is used if initial nursing interventions are not effective. Vasodilators frequently used are hydralazine, sodium nitroprusside, and nitroglycerin. Nicardipine has recently been introduced as an intravenous calcium channel blocker. Vasodilators are effective in BP reduction but may cause reflex tachycardia when used alone. Adrenergic inhibitors, such as esmolol and labetalol, block alpha and/or beta receptors to decrease heart rate and BP. Labetalol's effectiveness, relative freedom from side effects, and ease of administration have made it a useful drug in the treatment of APH.
 ...
PMID:Acute postoperative hypertension in the hypertensive patient. 173 70

The pathogenesis of hypertensive glomerular injury is complex, involving both hemodynamic and nonhemodynamic factors. One can therefore confidently predict that a wide variety of disparate therapeutic interventions, pharmacologic and nonpharmacologic, may be effective in arresting or slowing progressive glomerular injury. Based on the experimental and clinical literature available to date, it is clear that glomerular capillary hypertension is an important pathogenetic factor in this disease and that lowering of Pgc with antihypertensive drugs is associated with prevention of glomerular injury. Furthermore, the CEI may have a special renoprotective effect compared to other antihypertensive agents, most likely due to their unique renal hemodynamic actions. Pending the results of well-designed clinical trials, converting enzyme inhibitors represent the antihypertensive agents most likely to arrest the progressive decline in renal function observed in patients with hypertension and chronic renal failure. The calcium channel blockers are effective antihypertensive agents in patients with chronic renal failure, but whether they confer specific renoprotective effects remains uncertain. Since a large number of patients with chronic renal failure require more than one antihypertensive drug for adequate blood pressure control it may be of interest to evaluate the benefits of drug combinations. In this regard, it is possible that a combination of a CEI and a CCB may have complimentary effects in protecting the kidney. The development of these new classes of antihypertensive agents has had a major impact on the treatment of patients with chronic progressive renal failure. Future studies will hopefully clarify the optimal antihypertensive therapeutic regimen and allow us to move closer to the goal of eliminating end-stage renal failure.
 ...
PMID:Antihypertensive therapy and the progression of chronic renal disease. Are there renoprotective drugs? 174 81

The anti-hypertensive treatment of 631 patients 70 years old and over was evaluated at the time of their hospitalization in 12 Internal Medicine departments in the western Paris suburbs, in May and June 1990. 49.6 +/- 3.9% received no such therapy; 30.3 +/- 3.6% were being treated for hypertension (group 1); 8.7 +/- 2.2% were taking anti-hypertensive drugs for poorly specified reasons (group 2); 11.4 +/- 2.5% were under such treatment for another reason. In groups 1 or 1 + 2, the most frequently prescribed medications were, in decreasing order: diuretics, calcium channel blockers, converting enzyme inhibitors, beta-blockers or central inhibitors. In the oldest patients, the beta-blockers were prescribed less and converting enzyme inhibitors more. More than half of the patients in groups 1 + 2 were taking a single drug. The most frequently prescribed combined therapy was diuretic + converting enzyme inhibitor. Our results seem to indicate that the prescription modalities depended, for the most part, upon an associated or suspected pathology, notably cardiac insufficiency.
 ...
PMID:[Anti-hypertensive drugs prescribed to the elderly. Multicenter study at the hospital admission of 631 patients aged 70 plus years]. 177 82

We compared the antihypertensive effects and tolerability of a new calcium channel antagonist felodipine with nifedipine in an open randomised parallel group study in 49 patients with moderate hypertension (diastolic blood pressure 105-120 mm Hg). After two weeks run in period felodipine 5 mg and 10 mg once daily was compared with nifedipine 10 mg tid for an active treatment period of 4 weeks. Twenty three patients (mean age 42 +/- 10 years) received felodipine 5 mg once daily for first 2 weeks and 10 mg once daily for subsequent 2 weeks. Twenty six patients (mean age 45 +/- 9 years) received nifedipine 10 mg tid for 4 weeks. The mean reduction in supine diastolic blood pressure in two groups was 17 +/- 6 mm Hg (nifedipine) and 19 +/- 8 mm Hg (felodipine) (p = NS). The goal diastolic blood pressure of less than or equal to 90 mm Hg was achieved in 31 percent (nifedipine group) and 43.5 percent (felodipine group) of patients (p = NS). Side effects were common with both drugs; however, the tolerability was better with felodipine than with nifedipine. In conclusion felodipine was as effective as nifedipine and had the advantage of once a day dosage.
 ...
PMID:A parallel group randomised comparative study of felodipine and nifedipine in hypertension. 180 Mar 2

Loop diuretics are widely used drugs; serving to alleviate congestive heart failure and hypertension. Their mechanism of action is considered to be an inhibition of sodium retention in the kidneys, by a block of the Na/K/Cl cotransporter. The ensuing natriuresis and diuresis reduces blood pressure and alleviates congestive heart failure. Several earlier reports suggested direct cardiovascular effects, partly preceding the onset of diuresis. In the present study, evidence is presented for a direct action of two loop diuretic agents, bumetanide and furosemide, on cardiac L-type calcium currents in rabbit ventricular and atrial myocytes. This current is reversibly reduced by micromolar concentrations of these drugs. The onset of this effect can be observed within 1-2s, which could indicate a direct action on the calcium channel, independent of secondary effects subsequent to inhibition of the cotransporter. Thus, part of the therapeutic effects of the loop diuretics may be achieved through a direct reduction of cardiac output.
 ...
PMID:Loop diuretics block calcium currents in cardiac cells. 180 16

Effect of angiotensin converting enzyme inhibitor (ACEI) and calcium channel blockers (CaB) on renal blood flow (RBF), glomerular filtration rate (GFR), and autoregulation (AR) of RBF were studied on the uninephrectomized spontaneously hypertensive rat (SHR) under the conditions of high (H) and low (L) salt loading. SHR was given with 0.9% or 0.09% NaCl solution as drinking water (GH, GL). Each group was divided into three groups for treatment with enalapril (Enp) and nitredipine (Nit); i.e. Enp group (GHE, GLE), Nit group (GHN, GLN) and control group (GHC, GLC). After 6 weeks, inulin clearance (Cin) was determined and RBF was measured by means of an electromagnetic flow meter. The renal arterial pressure was lowered by clamping and changes in RBF and AR were examined. Cin showed higher values of 1.85 and 1.69 ml/min in GHN and GLN, as compared to be 1.33 and 1.28 ml/min in GHC and GLC (p less than 0.01). Filtration fraction (FF) showed lower values of 0.18 and 0.20 ml/min in GHE and GLE (p less than 0.01), whereas 0.29 and 0.30 in GHC and GLC respectively. RBF was markedly lower at 7.4 ml/min in GLC as compared to 9.9 ml/min in GHC (p less than 0.01). In GH, GHE showed a higher value of 11.6 ml/min, as compared to GHC (p less than 0.01). In GL, comparing with GLC the value was much higher of 12.1 ml/min in GLE (p less than 0.01). AR of RBF diminished in GLC at higher blood pressure as compared to GHC (p less than 0.01). It was maintained at lower blood pressure in GLE (p less than 0.01), but there were no significant differences between four groups; i.e. GLN, GHC, GHE and GHN. In summary, low salt loading reduced RBF and suppressed AR. Enp elevated RBF, lowered FF and caused AR to be maintained even at lower blood pressure. Nit elevated RBF and GFR without changing FF, and did not suppress AR. These results indicate that, in hypertension complicated with moderate dysfunction, both ACEI and CAB are expected to exhibit the beneficial effects on maintenance of renal circulation, despite though the different mechanism.
 ...
PMID:[Effect of angiotensin converting enzyme inhibitor and calcium channel blocker on renal function of spontaneously hypertensive rat]. 180 67

The cardiovascular effects of oxodipine, a new dihydropyridine calcium channel blocker, were studied after i.v. administration to chloralose-anesthetized dogs, and compared with those of nitrendipine. Nitrendipine produced more marked decreases than oxodipine in both systolic and diastolic blood pressure and in total peripheral resistance. No significant modification of heart rate was observed. Oxodipine decreased cardiac contractility, whereas nitrendipine increased it. This difference originated in reflex modifications, since both drugs, administered at doses of 30 and 60 micrograms/kg, decreased cardiac contractility during studies performed after cardiac autonomic blockade. Under these conditions, nitrendipine decreased heart rate, whereas oxodipine had no effect. The two drugs showed comparable effects on coronary and femoral vascular resistance. However, oxodipine caused a very marked persistent decrease of vertebral vascular resistance. On this local circulation, nitrendipine had a weak effect. The results from the present study indicate that oxodipine predominantly increases vertebral blood flow with a concomitant hypertension which is more moderate than after nitrendipine.
 ...
PMID:Cardiovascular profile of oxodipine, a novel dihydropyridine calcium channel blocker, in anesthetized open-chest dogs: a comparison with nitrendipine. 181 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>