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)

Twenty-six patients with hypertension secondary to acute poststreptococcal glomerulonephritis were treated by the rapid intravenous infusion of diazoxide. The average pretreatment systolic pressure was 159 mm Hg. Five minutes after administration, the average systolic pressure was 122 mm Hg (a 23% reduction). The average initial diastolic pressure was 104 mm Hg, which fell 5 minutes after diazoxide injection to 71 mm Hg (a 32% reduction). No hypotensive episodes were noted. Occasional episodes of nausea occurred. Concentrations of blood glucose increased after administration of diazoxide; however, no values were above 155 mg/dl. Diazoxide appears to be a safe antihypertensive drug that is effective in the treatment of hypertension secondary to acute poststreptococcal glomerulonephritis.
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PMID:Intravenous diazoxide in acute poststreptococcal glomerulonephritis. 118 52

Fourteen patients with severe hypertension have been given i.v. diazoxide in a dosage of 5 mg/kg b.wt. The material comprised 2 patients with malignant nephrosclerosis, 4 with chronic nephropathy and severe reduction of renal function, 1 patient with chronic pyelonephritis, 1 with renovascular hypertension and 6 patients with essential hypertension and in malignant phase. All patients attained a controllable blood pressure. Eight patients remaining needed only one injection, while the remaining patients required 2-5 injections, and concomitant furosemide therapy. The retinopathy improved in most patients and renal function was unchanged in the azotemic patients. No serious adverse effects were seen, except one hypotensive episode. Diazoxide is easy to handle, dosage can be predetermined, monitoring is simple and we find diazoxide to be a valuable drug in severe hypertension.
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PMID:Diazoxide in the management of severe hypertension. 119 11

Hyperpolarizing vasodilators that specifically activate ATP-sensitive K+ currents (IK(ATP] in smooth muscle have been suggested as promising antihypertensive (if potentially arrhythmogenic and/or hyperglycemic) therapy. To date, however, the effects of agents presumed to influence these channels have not been characterized in hypertrophied cardiac muscle secondary to chronic hypertension. We used standard intracellular and patch clamp, single-channel recording techniques to study the effects of diazoxide, a presumed activator, as well as the sulfonylurea glyburide on IK(ATP) in cardiac muscle from control (WKY) and spontaneously hypertensive rats (SHR). Intracellular recordings were obtained from isolated left ventricles at 37 degrees C; unitary currents were recorded in excised, inside-out membrane patches with symmetrical transmembrane K+ at 21-23 degrees C. Diazoxide (5-100 microM) caused a decrease in action potential duration in both WKY and SHR ventricles. Glyburide (5-25 microM) produced dramatic dose-dependent increases in action potential duration approaching 100% in both groups. Action potential amplitude and resting membrane potential were unaffected by either agent. Before drug administration, unitary currents in hypertrophied myocytes exhibited a greater open state probability upon depolarization than those from control myocytes, although conductance, mean single-channel open time, and the number of channels per patch were not significantly different. Under patch clamp, both diazoxide (25 and 100 microM) and glyburide (50 microM) decreased IK(ATP) activity in cells from WKY and SHR in the absence of ATP. In both groups, the response reflected an overall decrease in open state probability. These data indicate that although IK(ATP) characteristics are altered in hypertension and myocardial hypertrophy, the effects of agents specific to this current are not significantly different in cells from SHR relative to control. On the other hand, the effects of diazoxide may be linked to temperature or to the metabolic state of the cell.
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PMID:Effects of diazoxide and glyburide on ATP-sensitive K+ channels from hypertrophied ventricular myocytes. 153 Sep 75

The most important aspect of cerebral blood flow (CBF) in hypertension is the change that occurs in CBF autoregulation: increased cerebrovascular resistance causes the lower and upper limits of CBF autoregulation to be at higher pressure levels. The mechanism seems to be mainly structural thickening and luminal narrowing of cerebral resistance vessels. These adaptive changes, while protecting the brain against high intravascular pressure, render the brain more susceptible to ischemia at low blood pressure. An obvious consequence of the shift in the lower limit of CBF autoregulation in hypertension is that if the hypertensive patient's blood pressure is lowered acutely to "normal" levels, the pressure is below the patient's lower limit of autoregulation and ischemic damage may result. Basically, antihypertensive drugs can be placed into four groups as regards their effects on the cerebral circulation. First are the drugs without any direct effect: in this case, CBF remains constant until pressure reaches the lower limit of autoregulation and then decreases with any further pressure decrease. Diazoxide is in this category. Second are the drugs that directly dilate the small resistance levels in such a way that CBF is higher than normal at every pressure including pressures below the lower limit of autoregulation. However, perfusion may be uneven and autoregulation may be lost; an example of this kind of drug is dihydralazine. Third are the drugs which by alpha-or ganglion-blockade prevent the sympathetic vasoconstriction of large cerebral arteries (pial and larger), which can compromise CBF during a fall in blood pressure and hence shift the lower limit of autoregulation to a higher pressure than during blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral blood flow in hypertension. 240 78

Investigators using intracerebroventricular (ICV) injections of competitive antagonists of angiotensin II (Ang II) to study thirst usually select doses sufficient to block drinking to IV Ang II. We questioned whether this test truly indicates the dose needed under physiological conditions when Ang II-induced hypertension, which inhibits thirst, is not present. Rats were prepared with chronic venous and ICV cannulas, plus femoral arterial cannulas in those used to measure arterial pressure. Captopril (100 mg/kg SC) was given before all experiments to block endogenous Ang II production. The test dose of Ang II, 50 ng/kg/min IV for 1 hr, increased water intake and arterial pressure. We selected an ICV dose of saralasin (Sar1Ala8Ang II), 4 micrograms bolus and 4 micrograms/hr for 75 min, that did not stimulate drinking itself and completely blocked drinking to IV Ang II. This dose of saralasin only partially (45%) reduced drinking to the same dose of Ang II IV when arterial pressure was lowered by giving the vasodilator diazoxide (15 mg/kg IV). Diazoxide itself did not stimulate drinking. These results support our concern that the criterion normally used to select ICV doses of Ang II antagonists probably underestimates the amount needed to inhibit angiotensinergic drinking in hypovolemic or hypotensive animals.
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PMID:Test of a criterion for selecting intracranial doses of angiotensin receptor blockers. 259 Aug 42

Antihypertensive treatment may, for the same effect on hypertension, have a very different influence on the cerebral blood flow and the autoregulation curve. For instance, sodium nitroprusside, a potent vasodilator, risks to be poorly tolerated from the cerebral standpoint, when the sympathetic system is not inhibited. Diazoxide has no direct vasodilating effect on the cerebral vessels but, because of its marked hypotensive action must be used in divided doses. Hydralazine, a strong vasodilator, must be avoided in case of cerebral edema and hypertensive encephalopathy. Diuretics and beta-blockers, on a long-term basis, do not significantly modify the cerebral blood flow while alpha-methyl-dopa would increase it and facilitate a return to normal of the autoregulation curve. Captopril has demonstrated experimentally, interesting properties: in anaesthetized rats, it shifts the autoregulation curve to the left, i.e. toward lower pressures and it reduces the autoregulation curve to the left, i.e. toward lower pressures and it reduces the autoregulation limits; in awaken subjects, the decreased lower limit is also observed, explaining the good central tolerance of marked blood pressure reductions; on the contrary, its effects on the upper limit of the plateau are, unquestionably, counterbalanced by the effects of sympathetic stimulation concomitant with sudden blood pressure rises. As for calcium inhibitor, they do not seem to influence the long-term autoregulation of the cerebral flow.
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PMID:[The brain and arterial hypertension. 2. Effects of antihypertensive treatment on cerebral circulation]. 266 Jul 36

Treatment with intravenous and oral diazoxide was given to a group of 39 patients suffering from severe drug-resistant hypertension associated with renal impairment. Rapid initial and good long-term control of hypertension was achieved in all cases without the production of clinically significant postural hypotension. The side effects of diazoxide, including its diabetogenic effect, were easily controlled. There was a highly significant improvement in renal function in most patients on long-term oral diazoxide therapy.Diazoxide may have an important place in both the short- and long-term therapy of resistant hypertension, particularly in association with renal damage.
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PMID:Use of diazoxide in hypertension with renal failure. 511 16

Twenty-nine patients with severe hypertension (n = 14) or hypertensive crisis (n = 15) were treated with diazoxide infusion and intravenous injection of a beta blocker. In 13 patients diazoxide was administered first. It gradually reduced mean arterial pressure (MAP) by 16.1 +/- 2.1% (mean +/- SEM), and increased heart rate (HR) by 27.3 +/- 4.1% and plasma renin activity (PRA) by 48.9 +/- 13.0%. Beta blockade thereafter lowered MAP by only 1.2 +/- 1.9% despite reductions of HR by 35.6 +/- 2.2% and of PRA by 17.1 +/- 5.9%. In 16 other patients a beta blocker, when given first, reduced MAP by 3.5 +/- 1.2%, HR by 18.9 +/- 1.8%, and PRA by 24.2% +/- 4.4%. Diazoxide infusion thereafter gradually reduced MAP further by 21.9 +/- 1.9% and raised HR and PRA to pretreatment levels. No complications were observed. Beta blockade before diazoxide infusion effectively prevents a rise in HR above control levels while its acute effect on blood pressure is negligible. It is advisable to use this combined treatment in all situations where the occurrence of tachycardia might be dangerous.
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PMID:Combined intravenous administration of diazoxide and beta-blocking agent in acute treatment of severe hypertension or hypertensive crisis. 612 78

126 patients with blood pressure which was unacceptably high despite a conventional stepped-care regimen (diuretic, beta-blocker, and vasodilator) took part in a comparative assessment of different approaches to the treatment of refractory hypertension. One of four regimens was used: oral diazoxide, minoxidil, captopril, or quadruple therapy (diuretic + beta-adrenoceptor blocker + hydralazine + prazosin). Despite the severity of hypertension, blood pressure could be controlled in almost all these patients, and no patient died from cerebrovascular disease while on treatment. 2 patients died of renal failure and 5 patients required long-term haemodialysis. Ischaemic heart disease remained a problem and caused the death of 10 patients. Diazoxide was the most effective treatment but was the most difficult and unpleasant to use. Captopril was the best-tolerated but failed to control blood pressure in 6 of 15 patients. Our experience indicates that there are now sufficient therapeutic alternatives to achieve acceptable blood-pressure control in almost all patients with "refractory" hypertension, although no treatment is ideal.
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PMID:Treatment of refractory hypertension. 612 11

The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with renal and spontaneous hypertension. Diazoxide (5 mg/kg, i.v. bolus), caused arterial pressure to fall rapidly to that of normotensive rats, i.e. c. 75 mmHg. There was a concomitant fall in cerebral blood flow of about 35% (P less than 0.01) in renal hypertensive rats and 25% (P less than 0.05) in spontaneously hypertensive rats; the greater fall in flow in the former corresponded to a greater drop in pressure. Flow remained at these reduced levels during a 2 h observation period. Histological examination revealed small areas of ischaemic damage in the brains of five of the twelve animals. In control hypertensive rats not given diazoxide, cerebral blood flow and blood pressure were stable during a 2 1/2 h period and there was no evidence of ischaemic damage to the brains. The diazoxide-induced reduction in cerebral blood flow was interpreted as being secondary to a blood pressure fall to below the lower limit of cerebral blood flow autoregulation. No evidence was found of direct effects on the cerebral circulation such as seen with ganglionic blockers, alpha-blockers and cerebral vasodilators.
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PMID:Effect of diazoxide-induced hypotension on cerebral blood flow in hypertensive rats. 640 44


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