In previous studies, we established a strong concordance between nocturnal oscillations in plasma renin activity (PRA) and REM-NREM sleep cycles. To determine whether this relation persists in the case of moderate essential hypertension and if it is influenced by antihypertensive therapies affecting renin release, six normal subjects and six hypertensive patients were studied. The normal subjects underwent one control night. The hypertensive patients were studied during a first night when a placebo was given. Four of them underwent a second night following a single dose of an angiotensin-converting enzyme (ACE) inhibitor, perindopril; and a third night, 45 days later, with the antihypertensive treatment. In addition, two of the patients underwent two night-studies, after a single and repeated doses of a beta-blocker, atenolol, to see whether preventing renin release modified the sleep structure. The relationship between the nocturnal PRA oscillations and the sleep stage patterns persisted in hypertensive patients receiving placebo. In patients who had low PRA levels, the increases associated with NREM sleep were small. However, the mean relative amplitude of the oscillations, expressed as a percentage of the nocturnal mean, was about 60%, which was similar to that in normotensive subjects. Active renin and PRA oscillations were closely coupled. ACE activity profiles displayed damped fluctuations and no systematic relationship with sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

[Hyperthyroidism and immune hemolytic anemia following amiodarone therapy].

We report the cases of two patients who, after prolonged amiodarone therapy developed hyperthyroidism and immune haemolytic anaemia. Antibodies were of the IgG type and non-specific at elution. A search for other causes of haemolytic anaemia with positive Coombs' test gave negative results. Antiamiodarone antibodies have recently been discovered; they reflect an immunological disturbance due to this drug and might be responsible for some of the undersirable effects of amiodarone. In our patients, hyperthyroidism and haemolytic anaemia were induced by a dual mechanism: accumulation of amiodarone and induction of an effect of this drug on the immune system.

Aged↗

PubMedDate not supplied

Pharmacological characterization of renal vascular dopamine receptors.

We present an in vitro method for studying the renal effects of dopamine in the isolated rat kidney. The organ is perfused in an open circuit and can be maintained satisfactorily for up to 180 min. The responses to dopamine were studied in the presence of phenoxybenzamine (10(-5) M) and sotalol (10(-5) M) while stable renal vasoconstriction was maintained by perfusion with prostaglandine F2 alpha. Dopamine induced dose-dependent renal vasodilation with an ED50 of 2.53 X 10(-6) moles/liter, which was not modified by reserpine pretreatment. (+) Butaclamol but not (-) butaclamol shifted the dopamine dose-response curve to the right in a parallel fashion, indicating competitive antagonism. Haloperidol and sulpiride at concentrations without intrinsic effect on vascular resistance also acted as competitive inhibitors for dopamine. Calculation of empirical pA2 values yielded the following relative potencies for these antagonists: (+) butaclamol greater than haloperidol greater than sulpiride. The renal vascular dopamine receptors are tentatively classified as being of the D1 type.

Animals↗

PubMedDate not supplied

Blockade of dopamine receptors in the renal vasculature by isomers of flupenthixol and sulpiride.

We studied the renal vascular effects of flupenthixol and sulpiride isomers in the isolated perfused rat kidney in the presence of phenoxybenzamine (10(-5) M) and sotalol (10(-5) M). The vascular bed was contracted with prostaglandin F2 alpha (10(-7) -3 X 10(-6) M) and dose-dependently relaxed with dopamine. Cis-flupenthixol (10(-9)-10(-7) M) antagonized competitively the response to dopamine (apparent pA2 = 8.34 +/- 0.09; mean +/- SD) without affecting papaverine-induced relaxation. Trans-flupenthixol was without effect at 10(-7) M. The dopamine receptor antagonist activities of the sulpiride isomers are low and d-sulpiride is twice as active as 1-sulpiride. Thus, the renal vascular dopamine receptor can be further characterized by the relative antagonist activities of cis-flupenthixol and sulpiride and by a rather low stereospecificity in favor of d-sulpiride.

Animals↗

PubMedDate not supplied

Renal tissue angiotensins during converting enzyme inhibition in the spontaneously hypertensive rat.

To compare the effects of an angiotensin-converting enzyme inhibitor on circulating and tissue renin-angiotensin system (RAS), we measured different RAS parameters during the first day of treatment (Day1) as well as after two weeks of treatment (Day14). Ramipril was given orally once daily to adult male spontaneously hypertensive rats (SHR). Renin activity (RA), angiotensin converting enzyme (ACE) activity and levels of angiotensin I (ang I) and angiotensin II (ang II) in the plasma, renal cortex and renal medulla were assessed at Day1 and Day14 of the treatment. In the plasma, both RA and ang I increased 10 to 15 fold one to four hours after acute as well as at Day14 of ramipril treatment and then returned to basal values within 24 hours. Plasma ang II levels were not significantly decreased at Day1 or Day14. The decrease in the ang II/ang I ratio suggested a sustained inhibition of plasma ACE at Day14. In the renal cortex and medulla, a clearly different pattern was observed: in ramipril treated rats, RA in the renal cortex and medulla did not change at Day1 but at Day14 we observed a slight and sustained increase in RA. Despite very high basal levels of RA, ang I levels in the renal cortex were comparable to those in the plasma. The ang I level increased only one-fold one hour after ramipril intake at Day1 and Day14. This suggests that angiotensinogen may have a limiting role in the synthesis of ang I in the kidney. Ang II levels were slightly higher in the renal cortex and medulla than in the plasma suggesting local synthesis of the peptide. In the kidney, ang II levels decreased one and four hours after the acute or prolonged ramipril treatment and the ang II/ang I ratio was reduced at the same time. Our results show that the responses of the plasma and kidney components of the RAS to ACE inhibition are different in the plasma and the kidney suggesting that the circulating and tissue RAS are at least in part independent.

Angiotensin I↗

PubMedDate not supplied

[Iatrogenic medication: estimation of its prevalence in French public hospitals. Regional Centers of Pharmacovigilance].

The French network of Regional Centres of Pharmacovigilance has made an estimation of the occurrence of adverse drug reactions in a representative sample of patients in French public hospitals (departments of medicine, of surgery and of geriatrics). The study looked at one specific day in the spring of 1997. Each observed case of adverse drug reaction was validated. The total sample comprised 2132 patients of whom 969 were in a university hospital and 1163 in a general hospital. The hospitals and units concerned are representative of the country as a whole. One adverse drug reaction at least was present for 221 patients on the day of the investigation. This means a prevalence rate of 10.3 per cent (95 per cent CI: 8.7 to 11.9 per cent). In 33 per cent of cases (95 per cent CI: 26 to 42 per cent), the observed effects were rated as serious. From an incidence rate of 1.8 per cent (95 per cent CI: 1.0 to 25 per cent) on one specified day it can be estimated that in France an adverse drug reaction will occur in about 1,300,000 patients per year during a stay in hospital.

Adverse Drug Reaction Reporting Systems↗

PubMedDate not supplied

[Cost of hospitalizations for adverse drug effects].

The French network of Regional Pharmacovigilance Centres evaluated in 1997 the prevalence of adverse effects of drugs (AED). In 1998, and again with the support of the French Drug Agency, in collaboration with the company CEMKA for economic evaluations, the incidence of AED-related hospitalizations in the medical department of French public hospitals was studied. The evaluation was performed over 14 consecutive days in 62 hospital departments, which were selected randomly. The total number of 3137 patients were hospitalized for a mean duration of 9 days and they were using a mean number of six different drugs. Taking into account the number of about 4 million patients admitted per year in the hospitals represented, it was estimated that the total number of AED-related hospitalizations amounts to about 130,000 annually (CI95%: 100,916-156,620). Using established cost calculations for hospitalized days (AP-HP, results of 1996) the mean cost for an AED-related hospitalization was estimated to be about FF16,000.

Adult↗