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)

The complications of drug abuse encompass a spectrum of glomerular, interstitial, and vascular diseases. They comprise the heroin-associated nephropathy seen in African-American intravenous drug addicts, which, however, has given way in the 1990s to HIV-associated nephropathy. Infections with methicillin-resistant Staphylococcus aureus may cause acute glomerulonephritis by releasing bacterial superantigens. Hepatitis C has supplanted hepatitis B and may give rise to membranoproliferative glomerulonephritis and cryoglobulinemia. Addicts who inject drugs subcutaneously ('skin popping') may develop amyloidosis. Cocaine causes rhabdomyolysis, severe hypertension, occasionally renal failure in the absence of rhabdomyolysis, and may hasten progression to uremia in patients with underlying renal insufficiency. 'Ecstasy', an amphetamine-like recreational drug, has caused acute renal failure, electrolyte disturbances, and malignant hypertension. In Belgium and some other European countries, women taking Chinese herbs in a slimming regimen have developed a severe and irreversible interstitial fibrosis that is assuming epidemic proportions.
 ...
PMID:Drugs of abuse and renal disease. 874 32

Cocaine administration during pregnancy results in major maternal cardiovascular effects that in some cases exceed those observed in the nonpregnant state. Animal studies have shown increases in heart rate and blood pressure and decreases in regional organ blood flow. Fetal effects include arterial hypoxemia, increases in blood pressure and heart rate, and increases in cerebral blood flow that may be related not only to hypertension and hypoxemia, but also to direct effects on cerebral blood vessels. Fetal intestinal blood flow is decreased. These effects may be related to the clinical consequences of cocaine use during pregnancy.
 ...
PMID:Cardiovascular effects of cocaine during pregnancy. 885 96

To determine how the effect of insulin is related to the development of salt-induced hypertension, and whether a hyporesponse to insulin exists in the peripheral sympathetic nerves of a hypertensive model rat, we measured norepinephrine overflow from the periarterial nerve of isolated mesenteric arteries exposed to insulin in spontaneously hypertensive rats (SHR) as well as Wistar-Kyoto rats (WKY) fed diets that were high and low in salt. Salt loading (diet containing 8% salt for 4 weeks) accelerated the development of hypertension in young, spontaneously hypertensive rats (SHR) (157 +/- 5 mm Hg v 198 +/- 4 mm Hg, P < .01) but did not affect the blood pressure of Wistar-Kyoto rats (WKY) (102 +/- 7 mm Hg v 104 +/- 6 mm Hg, P = NS). Basal norepinephrine overflow did not differ in the SHR and WKY rats, but the overflow of norepinephrine after periarterial electrical stimulation (8 Hz 1 min.) was significantly greater in SHR (0.806 +/- 0.079 ng/g) than in WKY (0.723 +/- 0.022 ng/g; P < .01). Although insulin reduced the norepinephrine overflow by periarterial nerve stimulation in both WKY and SHR, the decrease with insulin was significantly greater in the SHR than in WKY (-18.4% +/- 4.0% v -32.0% +/- 4.6%, P < .05). The inhibitory effect of insulin on norepinephrine overflow was reduced by salt loading in SHR (-8.8% +/- 4.0%, P < .05), but not in WKY (-32.5% +/- 4.7%, P = NS). Cocaine and ouabain completely blocked the effect of insulin in all four groups. In contrast to insulin, direct stimulation of Na(+)-K+ ATPase with a high-potassium buffer (12 mmol/L) reduced NE overflow to the same extent among the four groups. These findings show that SHR have a blunted response to the suppression by insulin of norepinephrine overflow. Salt loading reduced the insulin response at peripheral sympathetic nerves of young SHR, but did not affect that of age-matched WKY. Thus, hyporeactivity to insulin may play a role in the development of salt-induced hypertension in young SHR, possibly through a reduced suppression of norepinephrine overflow from sympathetic nerve endings.
 ...
PMID:Effect of insulin on norepinephrine overflow at peripheral sympathetic nerve endings in young spontaneously hypertensive rats. 893 38

As cocaine abuse has become widespread, it has been associated with various cardiovascular complications, including angina pectoris, myocardial infarction, and sudden cardiac death. Cocaine's principal effects on the cardiovascular system are mediated via alpha-adrenergic stimulation and include (1) an increase in the determinants of myocardial oxygen demand (heart rate and systemic arterial pressure), and (2) a concomitant decrease in myocardial oxygen supply (caused by vasoconstriction of the epicardial coronary arteries). beta-adrenergic blocking agents may exacerbate cocaine-induced coronary arterial vasoconstriction, thereby increasing the magnitude of myocardial ischemia. In contrast, nitroglycerin and verapamil reverse cocaine-induced hypertension and coronary arterial vasoconstriction; therefore, they are the agents of choice in treating patients with cocaine-associated chest pain.
 ...
PMID:Cocaine-induced myocardial ischemia and infarction: pathophysiology, recognition, and management. 924 56

Cocaine is often used while consuming ethanol despite evidence that this combination may enhance the toxicity of cocaine. In the present study, we examined the cardiovascular effects of ethanol (475 or 950 mg/kg, i.v.) alone and in combination with cocaine (5 mg/kg, i.v.) in conscious rats. Ethanol or cocaine administration produced a consistent pressor response but highly variable cardiac output and systemic vascular resistance responses. The hemodynamic response patterns in individual rats to either drug were similar and related within rats. After ethanol pretreatment, cocaine produced greater decreases in cardiac output. We have proposed that this pattern of responses may reflect a predisposition in individual rats to cocaine-induced cardiomyopathies and hypertension. Furthermore, these data suggest that ethanol administration elicits a similar pattern of hemodynamic responses as previously reported for cocaine or amphetamine administration or acute behavioral stress.
 ...
PMID:Ethanol alters hemodynamic responses to cocaine in rats. 933 Sep 17

Cocaine causes acute hypertension by blocking catecholamine reuptake. There is evidence that it also impairs the peripheral endothelial nitric oxide system, which is normally vasodilatory. We further explored the role of nitric oxide in cocaine-induced vasoconstriction in anesthetized rats, and in vitro by using isolated carotid artery segments. Cocaine administered intravenously in rats increased mean arterial pressure by 30 to 40 mm Hg within 1 min. This effect was dose dependent and the maximum effect was observed at a dose of 1.25 mg/kg. The prototype catecholamine norepinephrine induced a similar increase in blood pressure. When rats were pretreated with NG-monomethyl-L-arginine (L-NMMA, a blocker of nitric oxide) and challenged with cocaine, the increase in blood pressure was blocked by 80%, whereas pretreatment with L-NMMA did not block norepinephrine-induced vasoconstriction. Both cocaine and norepinephrine also induced an immediate vasoconstriction in isolated carotid artery preparations. The in vitro vasoconstriction induced by cocaine was blocked by pretreatment with L-NMMA, whereas L-NMMA did not block the norepinephrine-induced vasoconstriction in vitro. Furthermore, carotid artery stripped of endothelium responded to norepinephrine but failed to respond to L-NMMA or cocaine. S-nitroso-N-acetyl-D,L-penicillamine (SNAP)-a precursor of nitric oxide- stimulated nitric oxide production in control coronary artery fragments. When these fragments were incubated with cocaine there was a 20% reduction in the production of nitrite oxide. These results suggest that cocaine exerts its peripheral vasoconstriction at least in part by inhibiting local vasodilator nitric oxide.
 ...
PMID:Role of nitric oxide in cocaine-induced acute hypertension. 965 30

The etiology of seizures associated with cocaine use is unclear. Because cocaine seizures are relatively uncommon, they should be diagnosed by exclusion and a neurological workup to rule out central nervous system (CNS) catastrophe should be made. This report describes the clinical findings, treatment, and blood cocaine and metabolite concentrations in a patient who, on two separate occasions, had seizures associated with crack cocaine ingestion. Approximately 1 hour after the ingestion incidents, the patient had multiple, generalized seizures that abated spontaneously. His workup for CNS bleeding, infection, and trauma was negative. Cocaine concentrations on the first incident peaked at 2.48 mg/L and on the second incident peaked at 3.9 mg/L. Other clinical findings included tachycardia, hypertension, diaphoresis, and disorientation. Blood cocaine and metabolite analysis revealed extremely high concentrations. Other than the incident of seizures and transient cardiovascular aberrations, these high concentrations were tolerated by the patient without further sequelae. A review of cocaine-induced seizures and treatment is included.
 ...
PMID:Multiple cocaine-induced seizures and corresponding cocaine and metabolite concentrations. 972 76

The association of cocaine and acute hypertension is well known; however, cocaine use has not generally been linked to chronic hypertension. We hypothesized that chronic use of cocaine over time would increase the prevalence of hypertension and that cocaine induced vasoconstriction would result in urine protein leakage, manifested by microalbuminuria. Therefore, we studied a population of predominantly black male patients admitted for addiction treatment whose drug of dependence was cocaine. A urine toxicology screen was considered positive if cocaine was detected within 24 h prior to or during admission to the hospital. A total of 301 patients with normal renal function were observed over their 2 week hospitalization. The majority (62%) of the patients were normotensive regardless of the status of their initial urine toxicology screen. Twenty percent of the population had acutely elevated blood pressure that normalized within 1 day, whereas 18% had blood pressure chronically >140/90 mm Hg (chronic hypertension). Levels of systolic and diastolic blood pressures were examined at age deciles and compared to the NHANES III (Third National Health and Nutrition Examination Survey) data for a predominantly black population. There was no significant difference in blood pressure with age in the cocaine users compared to the NHANES groups. Random urine samples were screened for the presence of microalbuminuria and no significant elevation was detected in any of the samples tested. We conclude that chronic cocaine use is associated with acute but not chronic hypertension in middle-aged black males. Cocaine use does not cause microalbuminuria.
 ...
PMID:Prevalence of hypertension in chronic cocaine users. 983 69

Cocaine is known to produce life-threatening cardiovascular complications in some but not all individuals. This review considers the premise that an appropriate animal model for cocaine-induced cardiotoxicity should be characterized by varying sensitivity in the population to the deleterious effects of cocaine. We have studied such a model in which physiological, biochemical, and pathological sensitivity to cocaine varies in rats. Our studies have identified a subset of rats that respond to cocaine with a decrease in cardiac output and a substantial increase in systemic vascular resistance (named vascular responders). In contrast, another group, designated mixed responders, is characterized by a smaller increase in systemic vascular resistance and a small increase in cardiac output. We reported that vascular responders are more likely to develop hypertension and cardiomyopathies with repeated cocaine administration. Under chloralose anesthesia, vascular responders have more profound pressor responses to cocaine and an initial brief spike in renal sympathetic nerve activity not usually noted in mixed responders. Vascular responders have higher resting and cocaine-induced dopamine turnover in the striatum. In addition, vascular responders have higher alpha-adrenergic vasoconstrictor tone, whereas mixed responders have higher adrenergic cardiac tone. The difference in cardiac output and systemic vascular resistance responses to cocaine in these two subsets of the population can be prevented by L-type calcium channel, muscarinic, or alpha-adrenergic blockade. Similar hemodynamic response variability is noted with other psychoactive agents and with acute stress, suggesting that the response patterns are not unique to cocaine. We propose that individual hemodynamic response variability is dependent on differences in CNS responsiveness and correlated with the incidence of cardiovascular disease.
 ...
PMID:Review of evidence for a novel model of cocaine-induced cardiovascular toxicity. 1041 92

Cocaine causes hypertension at least in part by stimulating the sympathetic nervous system, but it is not clear if this effect is centrally or peripherally mediated. To address this issue we studied the vasoconstrictive effect of cocaine in vivo and in isolated artery segments. In vivo cocaine increased mean arterial blood pressure (MAP) by 40 mmHg within 1 min of administration. Pretreatment with prazosin blocked this response by 62%. With clonidine the pre-cocaine MAP was lower and the hypertensive effect of cocaine was blocked by 50%, indicating an important role for central alpha-adrenergic mechanisms. In isolated rat carotid arteries cocaine-induced vasoconstriction was completely blocked by prazosin, phentolamine, and 6-hydroxydopamine, indicating a clear role for a peripheral effect. However, the relative contribution of the central alpha-adrenergic mechanism to the total vasoconstrictive response of cocaine was not clarified. 1999 Academic Press.
 ...
PMID:Cocaine-induced hypertension: role of the peripheral sympathetic system. 1043 72


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