Human physiological responses to immersion into water of different temperatures.

To differentiate between the effect of cold and hydrostatic pressure on hormone and cardiovascular functions of man, a group of young men was examined during 1-h head-out immersions in water of different temperatures (32 degrees C, 20 degrees C and 14 degrees C). Immersion in water at 32 degrees C did not change rectal temperature and metabolic rate, but lowered heart rate (by 15%) and systolic and diastolic blood pressures (by 11 %, or 12%, respectively), compared to controls at ambient air temperature. Plasma renin activity, plasma cortisol and aldosterone concentrations were also lowered (by 46%, 34%, and 17%, respectively), while diuresis was increased by 107%. Immersion at 20 degrees C induced a similar decrease in plasma renin activity, heart rate and systolic and diastolic blood pressures as immersion at thermoneutrality, in spite of lowered rectal temperature and an increased metabolic rate by 93%. Plasma cortisol concentrations tended to decrease, while plasma aldosterone concentration was unchanged. Diuresis was increased by 89%. No significant differences in changes in diuresis, plasma renin activity and aldosterone concentration compared to subjects immersed to 32 degrees C were observed. Cold water immersion (14 degrees C) lowered rectal temperature and increased metabolic rate (by 350%), heart rate and systolic and diastolic blood pressure (by 5%, 7%, and 8%, respectively). Plasma noradrenaline and dopamine concentrations were increased by 530% and by 250% respectively, while diuresis increased by 163% (more than at 32 degrees C). Plasma aldosterone concentrations increased by 23%. Plasma renin activity was reduced as during immersion in water at the highest temperature. Cortisol concentrations tended to decrease. Plasma adrenaline concentrations remained unchanged. Changes in plasma renin activity were not related to changes in aldosterone concentrations. Immersion in water of different temperatures did not increase blood concentrations of cortisol. There was no correlation between changes in rectal temperature and changes in hormone production. Our data supported the hypothesis that physiological changes induced by water immersion are mediated by humoral control mechanisms, while responses induced by cold are mainly due to increased activity of the sympathetic nervous system.

Association analysis of two tyrosine hydroxylase gene polymorphisms in normotensive offspring from hypertensive families.

OBJECTIVE: We have studied possible association between predisposition to essential hypertension, plasma noradrenaline level and two polymorphisms of the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. DESIGN AND METHODS: One hundred and one normotensive sons from normotensive parents (SN) and 107 normotensive sons of hypertensive families (SH) were studied. Tetranucleotide TCAT repeat and Va181Met polymorphisms of the TH gene were determined by polymerase chain reaction (PCR) technique. RESULTS: SH had higher systolic BP and plasma noradrenaline concentration than the SN group. No significant difference was found between the allele and genotype frequencies in the SH and SN groups for both polymorphisms. The two polymorphisms were in tight linkage disequilibrium. The CD genotype of the microsatellite marker was associated with increased plasma noradrenaline concentration in both groups. Genotypes AB, AE and BB of the TCAT repeat polymorphism and genotypes VM and MM of the Va181Met polymorphism exhibited the greatest difference in plasma noradrenaline concentration between the SH and SN groups. CONCLUSION: The studied TH polymorphisms do not appear to be associated with family history of essential hypertension. Nevertheless, some genotypes of TH might be related to disturbance of plasma noradrenaline concentration.

Utility of short-term heart rate variability for prediction of sudden cardiac death after acute myocardial infarction.

Heart rate variability (HRV) computed from 24-hour ECG recording has been associated with an increased risk of malignant arrhythmias after MI. To make HRV analysis more practical, we evaluated prospectively prognostic role of short-term HRV in comparison with other risk stratifiers. Study population consisted of 48 patients with acute MI (mean age 59.6 +/- 10.6 years, 38 males), who were off betablockers. All patients underwent 30-minute ECG recording at supine rest on day 2 and 5 after admission, between 9 and 11 a.m. One ECG channel from a commercial bedside monitor was A/D converted, and subsequently analysed using a purpose-built interactive software. Short-term HRV was computed as the standard deviation of all normal-to-normal RR intervals (SDNN) as well as the square root of the mean of the sum of the squares of differences between adjacent normal RR intervals (rMSSD). Left ventricular ejection fraction (LVEF, in %) was determined using 2D-echocardiography. During one-year follow up, 5 patients (10.4%) died of sudden cardiac death (SCD) and one of non-cardiac death. Subjects who died of SCD presented with significantly lower SDNN parameter on day 5 (28.8 +/- 4.3 vs 39 +/- 18.4, p < 0.006) and similar trend was revealed for rMSSD (12.22.8 vs 24.321, N.S.). Similarly, LVEF was significantly decreased in these patients (35.4 +/- 5.5 vs 49.7 +/- 11.3, p < 0.007). Positive predictive accuracy for prediction of SCD was 17% for rMSSD, 20% for SDNN, 29% for LVEF, and 40% for combination of depressed SDNN (< or = 33 ms) and LVEF (< or = 40). In conclusion, depressed HRV computed from short-term predischarge ECG recordings obtained under standardised conditions is associated with an increased risk of SCD. Such predictive power is substantially increased in combination with depressed LVEF, and this approach seems to be effective as a simple screening method to identify high risk subjects.

Metabolic, humoral and haemodynamic characteristics of normotensive offspring from hypertensive families.

Arterial hypertension is not only a haemodynamic abnormality, but it is associated with several metabolic and humoral changes. Heredity appears to be participating in the pathogenesis of essential hypertension (EH). We studied whether some metabolic, humoral and haemodynamic changes could be detected in genetically predisposed normotensive sons of hypertensive families (SH) compared with normotensive sons of normotensive parents (SN). The study groups consisted of 40 young SN and 40 SH matched for age and body mass index (BMI). Blood samples for laboratory determination were taken under basal conditions and 90 min after a 75 g glucose load. SH already had a higher systolic blood pressure (BP) (120.7 +/- 1.7 mm Hg) and a tendency to a higher diastolic BP than the SN group. In spite of the fact that both basal and stimulated glycemia did not differ significantly between the study groups, significantly higher glucose-stimulated immuno-reactive-insulin (IRI) was found in SH (80.1 +/- 7.06 vs 62.9 +/- 5.76 uU/l). Higher plasma concentration of catecholamines in SH indicate their higher sympathetico-adrenal activity. The groups did not differ significantly in basal and stimulated plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP). There was a tendency for higher levels of endothelin (ET) in the plasma of SH. The glucose load increased as expected, glycemia, IRI and C-peptide, but ANP and ET concentrations were unexpectedly reduced. These abnormalities were associated, in SH, with higher left ventricle (LV) mass index and impaired diastolic filling. Persistence of high LV mass index, even after adjustment for respective systolic BP, suggests the participation of more than haemodynamic stress in the increase of LV mass. Our results suggest that in normotensive genetically predisposed subjects from hypertensive families, some metabolic and humoral abnormalities can already be detected. They might be responsible for the higher BP readings with subsequent manifestations of hypertension and LV morphological and functional abnormalities.

Change in sympathetic activity, cardiovascular functions and plasma hormone concentrations due to cold water immersion in men.

The purpose of this study was to determine whether or not repeated short-term cold water immersions can induce a change in the activity of the sympathetic nervous system and, consequently, in cardiovascular functions in healthy young athletes. Changes in some plasma hormone concentrations were also followed. A single cold water immersion (head-out, at 14 degrees C, for 1 h) increased sympathetic nervous system activity, as evidenced by a four-fold increase (P < 0.05) in plasma noradrenaline concentration. Plasma adrenaline and dopamine concentrations were not increased significantly. Plasma renin-angiotensin activity was reduced by half (P < 0.05) during immersion but plasma aldosterone concentration was unchanged. Stimulation of the sympathetic nervous system during immersion did not induce significant changes in heart rate, but induced peripheral vasoconstriction (as judged from a decrease in skin temperature) and a small increase (by 10%) in systolic and diastolic blood pressures. No clear change in reactivity of the sympathetic nervous system was observed due to repeated cold water immersions (three times a week, for 6 weeks). Neither the plasma renin-angiotensin activity, aldosterone concentration nor cardiovascular parameters were significantly influenced by repeated cold water immersions. A lowered diastolic pressure and an increase in peripheral vasoconstriction were observed after cold acclimation, however. Evidently, the repeated cold stimuli were not sufficient to induce significant adaptational changes in sympathetic activity and hormone production.

Changes in proximal and distal coronary artery diameter during atrial pacing-induced myocardial ischemia.

BACKGROUND: The present study was designed to evaluate the role of tachycardia-induced dynamic coronary artery diameter changes in the development of myocardial ischemia. METHODS: Coronary angiography at rest and during atrial pacing-induced myocardial ischemia was performed in 22 patients. The diameter of the proximal and the corresponding distal coronary artery segments at rest and during pacing was measured using quantitative coronary angiography. Plasma levels of noradrenaline, adrenaline, dopamine and endothelin were determined in a subset of 14 patients in blood drawn from aorta and coronary sinus at rest and during pacing. RESULTS: Luminal diameter in normal proximal and distal segments increased, respectively, from 2.93 +/- 0.34 and 1.40 +/- 0.04 mm at rest to 3.03 +/- 0.25 and 1.58 +/- 0.07 mm during atrial pacing. The diameter of the proximal coronary artery segments with significant concentric stenosis decreased from 1.28 +/- 0.4 mm at rest to 0.95 +/- 0.34 mm during pacing, whereas segments with either significant eccentric or non-significant stenosis did not change significantly. A correlation was found between the noradrenaline level in the coronary sinus and the distal coronary artery diameter. CONCLUSIONS: A decrease in diameter of coronary artery segments with concentric stenosis during tachycardia might contribute to the development of myocardial ischemia. Some of the dynamic coronary artery changes may be influenced by the plasma level of noradrenaline. No evidence was found to suggest that dynamic changes in the diameter of proximal segments are related to the changes in diameter of the corresponding distal segments.

[Endothelin plasma levels in various stages and types of arterial hypertension]. / Plazmatická koncentrace endotelinu u ruzných stadií a typu arteriální hypertenze.

BACKGROUND: It can be assumed that endothelin (ET) the hitherto most powerful known vasoconstricting agent participates in the regulation of BP. The objective of this investigation was to compare ET plasma concentrations in different stages and types of arterial hypertension and to assess its possible participation in a rise of the BP. METHODS AND RESULTS: The authors assessed plasma concentration of ET1,2, using the RIA method, in 27 normotensive controls, 30 normotensive subjects with a family-history of hypertension, 21 patients with mild essential hypertension (EH), eight severe cases of EH and 27 patients with chronic renal failure who were in a regular dialyzation programe, incl. 13 treated on account of hypertension; in 14 the BP was within the normal range. The ET examination was supplemented by RIA assessment of the plasma renin activity (PRA). The authors recorded significantly higher ET concentrations as compared with controls (14.0 +/- 0.9 fmol/ml) in normotensive subjects from hypertensive families (18.1 +/- 1.2 fmol/ml), severe EH (26.1 +/- 3.2 fmol/l). Hypertensive patients with chronic renal failure (CHRS) had also higher ET levels (26.5 +/- 2.8 fmol/l). Patients with mild hypertension did not differ as regards ET concentrations (13.8 +/- 2.4 fmol/ml from controls. A significant increase of PRA was recorded in severe EH (3.4 +/- 1.2 ng/ml/hour) and in CHRS with hypertension (5.2 +/- 1.3 ng/ml/hour) as well as without hypertension (5.6 +/- 1.5 ng/ml/hour). CONCLUSIONS: The author's findings of elevated ET1,2 concentrations in subjects with a family disposition to hypertension, in advanced EH in renal hypertension and in CHRS support the assumption that ET can participate in the initial stages in the development and later in the progression of arterial hypertension either directly or by potentiating other pressor agents, e.g. higher activities of the renin-angiotensin system.

[Changes in humoral pressor and depressor factors in essential hypertension during lisinopril therapy]. / Zmeny presorických a depresorických humorálních faktoru u esenciální hypertenze pri lécbe lisinoprilem.

Arterial hypertension is nowadays no longer considered an isolated disorder of blood pressure regulation but a multifactorial disease with metabolic and cellular deviations. From the therapeutic aspect of thus conceived hypertension today inhibitors of the angiotensin converting enzyme seem most promising. With regard to their assumed comprehensive effect, the authors investigated simultaneously selected pressor and depressor humoral indicators and other indicators in 21 hypertensive patients with stage I and II of essential hypertension before and after three-month treatment with an angiotensin converting enzyme inhibitor lisinopril (Prinivil, Merck, Sharp and Dohme) and compared them with findings in 21 normotensive healthy subjects. Hypertensive subjects before treatment had, as compared with normotensives, significantly lower urinary kallikrein (7.8 +/- 1.2 < 18.0 +/- 4.2 EU/24hr, a significantly higher basal plasma adrenalin (1.27 +/- 0.20 > 0.54 +/- 0.20 pmol/ml) and adrenalin after a glucose load (1.26 +/- 0.22 > 0.51 +/- 0.12) and a higher relative plasma viscosity (1.74 +/- 0.02 > 1.67 +/- 0.01). The two groups did not differ significantly as to the plasma renin activity, plasma aldosterone and fibrinogen concentration and the level of urinary prostaglandins per 24 hr: 6-keto-prostaglandin F1a, thromboxane B2 and prostaglandins E and F2a. The 75 g glucose load produced an increased plasma renin, aldosterone and noradrenaline activity in normotensives as well as hypertensives before and after lisinopril treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Metabolic and humoral variations during the development of essential hypertension]. / Vývojové trendy metabolických a humorálních odchylek v prubehu vývoje esenciální hypertenze.

Some metabolic and humoral deviations found in normotensive offspring from hypertensive families can be modified in the course of years either as a result of ageing or of the clinical manifestation of essential hypertension (EH). The authors compared therefore some metabolic indicators (blood sugar level, IRI, C-peptide and plasma lipids) and humoral factors (plasma catecholamines, renin activity, atrial natriuretic factor and endothelin) in four groups of subjects: 27 young normotensive sons from normotensive families (SNF) and 30 from hypertensive families (SHF) with the findings of normotonics (NT) (n = 21) and patients with EH (n = 21) by 15 years older. Despite a tendency towards higher blood sugar levels in SHF and EH, the basal as well as oGTT stimulated blood sugar values were within the normal range. They were, however, associated with higher IRI and C-peptide concentrations in SHF with a further increase in NT and a much higher increase in EH. This indicates that normal blood sugar homeostasis in these groups is achieved only by an increased insulin secretion. The reduction of the blood sugar/IRI ratio in older NT accentuated in EH, suggests an increasing insulin resistance. In the lipid spectrum the authors found an increase of total cholesterol with advancing age, this being most marked in EH where also a decline of HDL cholesterol was recorded. As to humoral factors, higher catecholamine concentrations were found in SHF. Their increase with advancing age was more marked in EH. The plasma renin activity declined with age in NT as well as in EH.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelin concentrations in coronary sinus during atrial pacing-induced myocardial ischemia.

To investigate the possible role of endothelin in coronary vasoconstriction contributing to the development of myocardial ischemia, plasma endothelin concentrations at rest and during atrial pacing-induced myocardial ischemia have been measured in blood samples drawn from the aorta and coronary sinus in 12 patients with significant narrowing of the left anterior descending coronary artery. The plasma endothelin concentrations at rest were similar in the aorta (AO/R) and coronary sinus (CS/R) (4.8 +/- 2.4 and 4.5 +/- 1.7 pg/ml, respectively), the difference between coronary sinus and aorta plasma endothelin concentration (CS/R-AO/R) being -0.3 +/- 1.7 pg/ml. During atrial pacing-induced myocardial ischemia aortic plasma endothelin concentration (AO/P) did not change (4.6 +/- 2.6 pg/ml) and only an insignificant increase in the plasma endothelin concentration in the coronary sinus (CS/P) was observed (5.3 +/- 2.8 pg/ml). The difference between coronary sinus and aortic endothelin plasma concentration (CS/P-AO/P) was 0.6 +/- 2.5 pg/ml. Finally, the difference in endothelin concentrations between coronary sinus and aorta rose only insignificantly during pacing as compared to the resting values ([CS/P-AO/P]-[CS/R-AP/R] being 0.9 +/- 3.2 pg/ml). Thus, atrial pacing-induced myocardial ischemia in patients with significant left anterior descending coronary artery stenosis was not accompanied by significant changes in coronary sinus plasma endothelin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Metabolic and humoral characteristics of normotensive offspring in a family with a history of essential hypertension]. / Metabolická a humorální charakteristika normotenzních potomku s rodinnou zátezí esenciální hypertenze.

Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications.

[Control of hyperinsulinemia in essential hypertension using the angiotensin-converting enzyme inhibitor, lisinopril]. / Moznosti príznivého ovlivnení hyperinzulinémie u esenciální hypertenze inhibitorem angiotenzin konvertujícího enzymu lisinoprilem.

Hyperinsulinaemia and insulin resistance are associated with essential hypertension irrespective of obesity and non-insulin-dependent diabetes mellitus. One of the mechanisms whereby hyperinsulinaemia may play a role in the increase in blood pressure, is an increased activity of the sympathetic nervous system. The authors studied the incidence of hyperinsulinaemia, and the possibility of modulating it by 12-week administration of the ACE inhibitor (ACEI) lisinopril (Prinivil by MSD) at a dose of 20-40 mg/day. Compared with normotensive subjects, hypertensives showed a degree of hyperinsulinaemia and insulin resistance (higher blood glucose at higher immunoreactive insulin and C-peptide concentrations, and a higher IRI/blood glucose ratio) as well as manifestations of enhanced sympathetic activity (higher adrenaline levels). Lisinopril had a favourable effect not only on blood pressure but, also, on hyperinsulinaemia and adrenaline levels. It can be reasonably concluded that therapy with ACEI, in addition to its antihypertensive effect, may also favourably modulate some pathogenic and metabolic factors in essential hypertension.

Plasma concentrations of some cardiovascular humoral factors in essential hypertension and their changes during the treatment with converting enzyme inhibitor lisinopril.

Plasma concentration of two main cardiovascular substances - atrial natriuretic factor (ANF) and endothelin - were studied in control subjects (n = 21) under basal conditions and 90 minutes after oral administration of glucose. In hypertensive patients (n = 21) these determinations were repeated after 12 weeks treatment with an angiotensin I-converting enzyme inhibitor lisinopril (Prinivil, Merck Sharp and Dohme). While basal and post-glucose ANF concentrations did not differ in controls and hypertensive patients, a tendency to the higher endothelin levels was found in our group of essential hypertension when compared to normotensive subjects. Glucose loading did not change significantly ANF concentrations in any studied group but significantly lowered plasma endothelin in both controls (from 13 +/- 0.95 to 9.50 +/- 0.95 fmol/ml) and hypertensive patients (from 15.05 +/- 1.23 to 12.15 +/- 1.03 fmol/min). Treatment of hypertensive patients with lisinopril paradoxically increased concentrations of ANF (from 6.43 +/- 2.53 to 11.47 +/- 4.90 fmol/ml) and lowered that of endothelin (from 15.05 +/- 1.23 to 12.17 +/- 1.58 fmol/ml). From our findings we may suggest that the relative predominance of the vasoconstrictor (endothelin) over the vasodilator (ANF) humoral substances might participate in pathogenesis of EH and that the reversal of this disadvantageous ratio after lisinopril (increase of ANF and decrease of endothelin) might contribute to the blood pressure reducing effect of ACEI. The drop in plasma endothelin after glucose remains so far unexplained consequence of glucose loading in both control and hypertensive subjects.

Relationship between plasma catecholamines and the renin-aldosterone system during exercise in normal and essential hypertensive subjects.

Interrelations were investigated between blood pressure, plasma epinephrine (E), norepinephrine (NE), dopamine (D), aldosterone, cortisol concentrations, active and inactive plasma renin activity (PRA), and age in 21 normotensive subjects (aged 20-60 years) and in 25 patients (aged 20-63 years) with essential hypertension (EH). These parameters were measured at rest and during exercise on a bicycle ergometer. In normotensive subjects basal and exercise-stimulated levels of plasma NE increased with age which was not observed in EH. In hypertensive patients there was a higher plasma D concentration under the exercise as compared with normotensive controls. In the normotensives, basal active PRA was inversely related to age (p less than 0.05), and during initial 8 min of exercise active PRA significantly correlated with plasma E and plasma NE. Moreover, absolute changes from basal to acutely stimulated values of active PRA were directly related to the changes of plasma E and NE (p less than 0.001). In hypertensive patients these relationships were not found. However, in the hypertensives there were significant positive correlations between the increases of active PRA, plasma E, plasma NE on the one hand and their respective basal values on the other hand. The results indicate very strong functional relationship between the sympathetic-adrenomedullary and renin-angiotensin systems during initial interval of acute stimulation in normotensive subjects. Essential hypertension is not a pathophysiologically homogenous disease with respect to reactivity and interaction of plasma catecholamines and PRA. Separate regulatory pathways exist for plasma active and inactive renin. During short-time exercise aldosterone secretion is related rather to the renin-angiotensin system than to the hypothalamic-pituitary axis.

Interrelations between plasma renin activity, aldosterone, and sympathetic nervous system activity in essential hypertension.

Interrelations were investigated between plasma renin activity (PRA), dopamine-beta-hydroxylase activity (DBH), plasma aldosterone (PA), plasma cortisol (PC) and plasma sodium concentration (PNa) in renal vein blood of essential hypertension patients in recumbent position. The patients were divided in compliance with the WHO classification into two groups of stage I and stage II of essential hypertension. In stage I a negative correlation was found in all samples of blood between PA and PNa. This means that in recumbent position in stage I the mechanism of regulation sodium -- aldosterone is maintained. In stage II there were very significant correlations between DBH and PRA in the samples from both renal veins. The left renal vein blood gives the best information about secretion of the left adrenal gland. In stage II in samples from the left renal vein a negative correlation was proved between PA and PRA, and also two very similar negative correlations PA -- DBH and PC -- DBH were demonstrated. The results indicate that in recumbent position in stage II the renin secretion is mainly under the control of the sympathetic nervous system, even if the activity of the latter is depressed, normal or enhanced. The possible negative relation between sympathetic activity and corticosteroid secretion in stage II of essential hypertension is discussed.