[Serious intoxication after inhaling methanol]. / Ernstige intoxicatie met methanol door inhalatie.

A 38-year-old man presented with severe methanol intoxication after inhaling methanol over a period of 36 hours in a poorly-ventilated laboratory. He complained of visual disturbances, mild photophobia, hyperventilation and nausea. Laboratory results showed severe metabolic acidosis with a toxic serum-methanol level. He was treated by acute haemodialysis and ethanol infusions. After 9 hours of haemodialysis the serum-methanol value fell below toxic levels. Therapy resulted in the complete disappearance of symptoms and he was able to leave the intensive-care unit 24 hours after presentation. Often, late presentation is a cause of serious morbidity and even mortality in severe methanol intoxication, so early recognition is essential. This is the first published case of methanol intoxication due to inhalation, which is as serious and requires the same treatment as ingestion of methanol.

Microvascular effects of atrial natriuretic peptide (ANP) in man: studies during high and low salt diet.

OBJECTIVE: Infusion of ANP in anephric dogs causes a decrease in cardiac output and a rise in peripheral vascular resistance. This reduced cardiac output is possibly related to increased resistance to venous return generated in the microcirculation by venular constriction. The aim of the present study was to evaluate in healthy volunteers the effects of low-dose ANP infusion on both conjunctival and skin microcirculation during high or low salt diet. METHODS: ANP (7.5 ng/kg/min) and placebo were infused (i.v.) for 4 h, in random order on two separate days, in two groups of 10 healthy male volunteers each. One group was studied during high salt (ad libitum), and one group during low salt (55 mmol Na+/24 h) diet. Microvascular density and diameters of both conjunctiva and nailfold were studied using intravital videomicroscopy. Nailfold capillary red blood cell velocity (CBV) was studied using intravital videomicroscopy, and skin (thermoregulatory) blood flow (SBF) was studied using laser-Doppler fluximetry. RESULTS: In the high salt group ANP induced a 43% reduction in basal SBF as compared to an 18% reduction by placebo (P < 0.01). Parallel to SBF, ANP significantly reduced CBV (P < 0.02). Conjunctival capillary density decreased by 5% during ANP, while it increased by 28% during placebo (P < 0.05). No such effects of ANP were observed in the low salt group. Blood pressure and heart rate were not influenced by ANP infusion in neither group. CONCLUSION: Infusion of low doses of ANP into humans on an ad libitum salt diet results in vasoconstriction of the microcirculation, probably on the venular side. The lack of effect of ANP on the microcirculation during low salt diet may be related to a higher vascular tone prior to infusion.

Dissociation between the renal effects of angiotensin I and II in sodium-restricted normal subjects.

OBJECTIVE: To determine whether the effects of angiotensin I (AngI) in humans can be explained entirely by its plasmatic conversion to angiotensin II (AngII). METHODS: Ten healthy male volunteers on a sodium-restricted diet were studied on two separate occasions. during which, in random order, AngI or AngII was infused in increasing doses of 0.3, 1 and 3 pmol x kg-1 x min-1. Mean arterial pressure (MAP), effective renal plasma flow (ERPF), glomerular filtration rate (GER), active plasma renin concentration (APRC), AngII, aldosterone (Aldo) and catecholamines were assessed at baseline, after each dose of AngI or AngII and 30 and 60 min after discontinuation of the AngI/AngII infusion. RESULTS: The rise in plasma AngII was significantly less during AngI infusion as compared to AngII infusion (P < 0.05). Changes in MAP, Aldo and GFR, however, were compatible during both infusions. In the kidney, on the other hand, the decrements in APRC and ERPF during AngII infusion exceeded those during AngI (P < 0.05). After cessation of either infusion. AngII concentrations, MAP, ERPF and Aldo returned to baseline levels within 1 h. Renin, however, was still significantly inhibited at that time (P < 0.05). Catecholamines remained virtually unchanged during all experiments. CONCLUSIONS: Our data show that AngI and AngII have similar effects on blood pressure and Aldo, but they differ in their renal effects. The latter may be due to a low renal capacity to convert AngI. The prolonged inhibition of renin release after cessation of the infusions may be caused by reduced renin mRNA expression or by accumulation of AngII in the kidney.

Sensitivity of blood pressure and renin activation during sodium restriction.

The objective of the present study was to explore the interrelationships among cumulative sodium loss, renin activation, and blood pressure changes during sodium restriction in essential hypertensive patients. Specifically, we wanted to know whether the degree of sodium sensitivity of blood pressure depends on renin activation during steady state or on initial renin activation during the first days of sodium restriction. Sixty-seven untreated essential hypertensive patients were admitted to a metabolic ward for 8 days and put on a sodium restricted diet of 55 mmol/d from the second to the last day. Urinary excretions of sodium, potassium, and creatinine were determined along with mean arterial pressure and weight during 7 days. Besides measurements in steady state condition (after 7 days), active plasma renin concentration, aldosterone, and catecholamines were also assessed during the first 3 days of sodium restriction. Analyzable data are available for 55 patients. Baseline sodium excretion and the activation of renin during the first 3 days both appeared to be predictors of total sodium loss after 7 days. Changes in blood pressure were not related to changes in sodium balance, but they were to baseline blood pressure, baseline norepinephrine, and renin activation during the early phase of sodium restriction. In addition, blood pressure appeared to fall more when the normal relationship between sodium loss and early (but not late) activation of renin was disturbed. We conclude that sodium sensitivity of blood pressure during sodium restriction is associated with a relative unresponsiveness of the renin system during the early phase of sodium loss rather than to absolute renin levels during steady state.

Natriuretic effect of nitrendipine is preceded by transient systemic and renal hemodynamic effects.

This study investigated whether the acute natriuretic effect of nitrendipine is related to its initial renal hemodynamic effects. We investigated 16 patients (10 men and 6 women, mean age 52 +/- 2 years) with essential hypertension, whose treatment, if any, was stopped 3 weeks before the study. They were admitted to a metabolic ward for 9 days and kept on a constant sodium diet of 55 mmol/day. During two 24-hour experiments, subjects randomly received a single oral dose of placebo/nitrendipine 10 mg (group 1, n = 8) or placebo/nitrendipine 20 mg (group 2, n = 8), according to a double-blind crossover study design. Patients fasted during the experiments, but their sodium intake was ensured by a constant intravenous saline infusion of 2.3 mmol/hr. Mean arterial pressure (MAP) and heart rate were determined for 5 hours following the administration of nitrendipine or placebo. Effective renal plasma flow (ERPF), glomerular filtration rate, active plasma renin concentration, angiotensin II, aldosterone, atrial natriuretic peptide, and catecholamines were determined every hour for 5 hours. Hourly urine collections were used to assess sodium, potassium, and creatinine excretions. Relative to placebo, only in group 2 (nitrendipine 20 mg) was a fall in MAP and a rise in ERPF observed 2 hours after the start of the experiment. The effects, however, lasted only for 1 hour. No such changes were seen in group 1. In neither group did nitrendipine affect hormonal concentrations. Sodium excretion was enhanced after the 20-mg dose of nitrendipine only (p < 0.05). Nitrendipine 20 mg induced a significant increase in sodium excretion, which may be dissociated from its acute hemodynamic effects.

[Salt sensitive blood pressure and the renin-angiotensin system in hypertension]. / Zoutgevoelige bloeddruk en het renine-angiotensinesysteem bij hypertensie.

The relationship between (excessive) use of sodium chloride and the blood pressure is still equivocal. Blood pressure responses to alterations in dietary salt consumption vary greatly between individuals, which has led to the concept of salt sensitivity. Although the mechanisms which determine the degree of salt sensitivity are not fully understood, the renin-angiotensin system seems to play a key role. A relative inability of this system to respond promptly to alterations in salt intake may underlie the development of salt sensitivity. By administering drugs which block the renin-angiotensin system to patients with essential hypertension, blood pressure is rendered more sensitive to the effects of salt restriction and (or) diuretic treatment.

Heterogeneous patterns of sodium excretion during sodium restriction in essential hypertensive patients.

OBJECTIVE: To study the sodium excretory pattern by which sodium balance is reached. METHODS: Ninety untreated essential hypertensives with a median age of 47 (range: 18-70 years) were admitted to a metabolic ward for 7 days and put on a sodium diet of 55 mmol/day. During these 7 days urinary excretions of sodium, potassium and creatinine were determined daily along with mean arterial pressure (MAP) and weight. RESULTS: Changes in urinary sodium excretion were not uniform, but according to the pattern of attaining sodium balance, subjects could be divided into four groups. Group 1 (n = 31) gradually reached sodium balance, whereas group 2 (n = 10) showed an abrupt fall in sodium excretion on the third day and an extremely fluctuating sodium excretion thereafter. Group 3 (n = 32) reached sodium balance on day four, but displayed a rise in sodium excretion during the following days and group 4 (n = 17) attained sodium balance only very slowly or not at all. Compared to the other groups, group 4 lost more sodium and at the same time displayed a greater fall in blood pressure. CONCLUSIONS: Our data suggest that there may be at least four different patterns by which sodium balance can be reached following a reduction in sodium intake. The determinants of these responses remain, however, elusive.

Sodium sensitivity of blood pressure in hypertensives is not related to sodium, but rather to renin.

OBJECTIVE: To investigate whether a certain degree of sodium-sensitivity of blood pressure (BP) in essential hypertensives during sodium restriction is related to cumulative sodium loss. METHODS: One-hundred and seventeen untreated essential hypertensives were admitted to a metabolic ward for 7 days and put on a sodium restricted diet of 55 mmol/day. During these 7 days urinary excretions of sodium, potassium and creatinine were determined daily along with mean arterial pressure (MAP) and weight. Active plasma renin concentration (APRC), aldosterone (ALDO), renal plasma flow (RPF) and plasma volume (PV) were assessed after 7 days under steady state condition. The population was divided into tertiles based on the final changes in BP after 7 days. RESULTS: Textile 1 displayed a median fall in MAP of -13 (-42 to -9) mm Hg, whereas in tertile 2 and 3 a fall of -6 (-9 to -4) mm Hg and a rise of +1 (-3 to +11) mm Hg respectively, was encountered. Baseline characteristics were comparable between the tertiles. When tertile 1 was compared to tertile 3 no significant differences between these tertiles were found with respect to cumulative sodium and potassium balances and weight loss. Furthermore, APRC levels were significantly higher in tertile 3 as compared to tertile 1 (22 and 27 mU/l, respectively). Renal vascular resistance (RVR) tended to be higher in tertile 3, although this was not statistically significant. Aldo, RPF and PV were comparable between the tertiles. CONCLUSIONS: In contrast with tertile 1, MAP in tertile 3 is maintained at its original level, despite comparable sodium losses. In tertile 3, however, levels of renin are higher compared to the group that is more sodium-sensitive. Therefore, our data suggest that the degree of sodium-sensitivity of BP in essential hypertensive subjects is not determined by sodium status, but rather by renin.