Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension.

BACKGROUND: Rarefaction of skin capillaries in people with intermittent borderline essential hypertension suggests a primary or an early abnormality that may antedate the onset of sustained hypertension. OBJECTIVE: To compare skin capillary density in subjects with and without a family history of essential hypertension. SUBJECTS: 21 normotensive individuals, one or both of whose parents had essential hypertension (mean age 39.3 years; blood pressure 124/79 mm Hg); 21 normotensive controls with no family history of hypertension (age 46.3 years; blood pressure 124/78 mm Hg). METHODS: The skin of the dorsum of the fingers was examined by intravital capillary microscopy before and after venous congestion at 60 mm Hg for two minutes. RESULTS: By analysis of variance, both baseline and maximum skin capillary density were lower in subjects with a family history of essential hypertension than in those with no family history (baseline: 67 v 79 capillaries per field, p = 0.008; maximum: 74 v 93 capillaries per field, p < 0.0005). CONCLUSIONS: Capillary rarefaction in essential hypertension may occur before the increase in blood pressure and could, at least in part, reflect a primary rather than a secondary abnormality.

Effect of salt intake on renal excretion of water in humans.

Two studies were performed to determine the quantitative relationship between salt intake and urinary volume (U(v)) in humans. In study 1, 104 untreated hypertensives were studied on the fifth day of a high- and a low-salt diet. The 24-hour U(v) was 2.2 L (urinary sodium [U(Na)] 277 mmol) on the high-salt diet and decreased to 1.3 L (P<0.001) (U(Na) 20.8 mmol) on the low-salt diet. The reduction in 24-hour U(v) was significantly related to the decrease in 24-hour U(Na) (P<0.001) and predicts that a 100-mmol/d reduction in salt intake would decrease 24-hour U(v) by 367 mL. In study 2, 634 untreated hypertensives were studied on their usual diet. There was a significant relationship between 24-hour U(v) and U(Na) (P<0.001). This predicts that a 100-mmol/d reduction in salt intake would decrease 24-hour U(v) by 454 mL. The International Study of Salt and Blood Pressure (INTERSALT) of 1731 hypertensives and 8343 normotensives on their usual diet showed that 24-hour U(v) was significantly related to U(Na) (P<0.001) and predicted that a 100-mmol/d reduction in salt intake would decrease 24-hour U(v) by 379 and 399 mL in hypertensives and normotensives, respectively. These findings document the important effect that salt intake has on U(v). The recommended reduction in salt intake in the general population is from 10 to 5 g/d. This would reduce fluid intake in the population by approximately 350 mL/d per person. This would have a large impact on the sales of soft drinks, mineral water, and beer.

Importance of the renin system for determining blood pressure fall with acute salt restriction in hypertensive and normotensive whites.

Hypertensive (n=93) and normotensive (n=39) white individuals were given a high sodium intake of approximately 350 mmol/d for 5 days followed by a low sodium intake of 10 to 20 mmol/d for 5 days. With this acute and large reduction in salt intake, no significant change was seen in blood pressure in the normotensive individuals, but blood pressure decreased in the hypertensive individuals. Compared with normotensive subjects, hypertensive patients had a 7/7-mm Hg greater fall in blood pressure (P<0.05 for systolic and P<0.01 for diastolic, adjusted for age), with similar changes in urinary sodium excretion. From the high-salt to low-salt diet, plasma renin activity rose from 0.90 to 5.99 ng. mL(-1). h(-1) in normotensives, whereas in hypertensives it rose from 0.73 to only 3.14 ng. mL(-1). h(-1) (P<0.05 between hypertensives and normotensives). Plasma aldosterone rose by 1396 pmol/L in normotensive subjects and by 511 pmol/L in hypertensive patients (P<0.05). Significant inverse correlations were obtained for all subjects between the fall in blood pressure from the high-salt to low-salt diet and the rise in plasma renin activity and aldosterone that occurred in addition to the absolute level on the low-salt diet. These results demonstrate that the larger fall in blood pressure with an acute reduction in salt intake in hypertensives compared with normotensives is, at least in part, due to a less-responsive renin-angiotensin-aldosterone system in the hypertensive patients.

In-vivo intracellular pH at rest and during exercise in patients with essential hypertension.

BACKGROUND: Several studies in isolated cells have reported that intracellular pH (pHi) in individuals with essential hypertension may be relatively alkaline compared to normotensive individuals. Such an abnormality of pHi in hypertension would be consistent with enhanced sodium-hydrogen exchanger activity and may provide potential mechanisms by which hypertension and its complications could develop. OBJECTIVES: To determine in-vivo intracellular pH of skeletal muscle at rest and during recovery from exercise-induced acidosis in hypertensive and normotensive subjects. METHODS: Using 31-phosphorus magnetic resonance spectroscopy, pHi of the dominant flexor digitorum superficialis was measured in 20 Caucasian subjects (14 male) with essential hypertension and 20 normotensive controls matched for gender, age, race and body mass index. Measurements were made at rest and during the exercise and recovery periods of a stepped incremental maximal exercise protocol. The rate of pHi recovery from exercise-induced acidosis was calculated by linear regression over the first 210 s of recovery from the pHi time plots of respective subjects. RESULTS: Mean resting pHi in the hypertensive (7.05 +/- 0.04) and normotensive groups (7.06 +/- 0.04) were not significantly different. There was a significant effect of gender on pHi: mean pHi was 7.07 +/- 0.03 in males and 7.02 +/- 0.03 in females, respectively (P < 0.0005). The mean intracellular pH achieved by exercise was 6.74 +/- 0.31 in hypertensive individuals and not significantly different in normotensive individuals (6.68 +/- 0.19; P = 0.4). The mean rate of pHi recovery in the hypertensives was 0.08 +/- 0.03 pH units/min and not significantly different in normotensives (0.08 +/- 0.02; P = 0.4). CONCLUSIONS: These results contrast with previously documented abnormalities in the control of pHi in hypertension and demonstrate the absence of major in-vivo disturbances of pHi in skeletal muscle, both at rest and during recovery from exercise-induced acidosis, in essential hypertension. Therefore, it is possible that previously documented abnormalities of pHi and activity of the exchanger may be either specific to cell type or not present under in-vivo conditions.

Platelet sodium-hydrogen exchanger activity and left ventricular mass.

INTRODUCTION: The sodium-hydrogen exchanger (NHE) is integral to the processes that facilitate cell growth and may contribute to the development of left ventricular hypertrophy. The aim of this study was to examine the relationship between platelet sodium-hydrogen exchanger activity and left ventricular mass index (LVMI). METHODS: Twenty male untreated Caucasians (mean age +/- s.d.: 48 +/- 13; body mass index: 29 +/- 4 kg/m(2)) with a wide range of blood pressures were studied (mean BP: 152 +/- 22/93 +/- 15 mm Hg; range: 115-190/61-117 mm Hg). Sodium-hydrogen exchanger activity was determined as the rate of sodium-dependent recovery of intracellular pH in isolated platelets loaded with BCECF and acidified to pH 6.25 using nigericin. LVMI was calculated from measurements made by M-mode echocardiography. Associations between continuous variables were examined using parametric tests. RESULTS: The mean rate of pHi recovery was 0.15 +/- 0.03 dpHi/s (range: 0.09-0.21). Mean LVMI was 120 +/- 32 g/m(2) (range: 56-178) and was not significantly correlated with either systolic (r = 0.39, P = 0.09) or diastolic blood pressure (r = 0.27, P = 0.3). Platelet NHE activity was not significantly correlated with LVMI (r = 0.06; P = 0.8). Platelet NHE activity was not significantly different between subjects with (n = 7 with LVMI >131 g/m(2)) and without left ventricular hypertrophy (n = 13). CONCLUSIONS: The results of this study show that platelet NHE activity is not significantly correlated with LVMI. These data contrast with previously described correlations of LVMI with exchanger activity measured in leucocytes and erythrocytes; and indicate that the relationship between LVMI and exchanger activity may be specific to the cell type in which exchanger activity is measured.

Transepithelial sodium absorption is increased in people of African origin.

Salt-sensitive hypertension is more common and has more severe consequences in urban black populations than in white populations. Increased renal sodium reabsorption through epithelial sodium channels may underlie the development of high blood pressure in black people. Increased sodium channel activity has been detected in subjects with Liddle's syndrome by nasal potential difference measurements. Nasal potential difference measurements were made in 39 black normotensive, 106 black hypertensive, 51 white normotensive, and 61 white hypertensive subjects. Blood pressure, body mass index, and 24-hour urinary sodium excretion were also measured. Maximum potential difference was significantly higher in black subjects than in white subjects (P=0.009) but was not significantly different between normotensive and hypertensive subjects after adjustment for age, gender, current smoking status, body mass index, and 24-hour urinary sodium excretion (black normotensive, -21.6+/-1.0 mV; black hypertensive, -21.5+/-0.7 mV; white normotensive, -18.5+/-1.0 mV; and white hypertensive subjects, -18.9+/-0.9 mV). Nasal potential difference did not correlate with blood pressure or biochemical variables within ethnic and blood pressure groups. Nasal potential difference, an index of nasal sodium channel activity, is greater in black than in white people but does not differ between normotensive and hypertensive groups. Increased nasal potential difference measurements may reflect generalized upregulation of sodium transport in black people compared with white people, which may help to explain the high prevalence of hypertension in black people but would not explain differences in blood pressure within separate ethnic groups.

Ethnic differences in erythrocyte membrane fluidity and the association with serum triacylglycerols.

The objectives of this study were to determine whether there are differences between black and white individuals with regard to the membrane fluidity of isolated erythrocytes, and/or in the relationships between membrane fluidity, gender and circulating lipids. Fluorescent polarization anisotropy, as an index of membrane fluidity, was determined using the fluorescent probe 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in 52 black and 52 white individuals, of whom 39 pairs were matched for age, sex and blood pressure. In the 39 matched pairs, the TMA-DPH anisotropy was significantly higher in the black (0.262+/-0.007) compared with the white (0.258+/-0.005) subjects (P<0.005). There was also a significant difference in serum lipids. Gender differences in TMA-DPH anisotropy were observed in the white but not in the black individuals. The associations between membrane fluidity and serum lipids were examined in the total group, separated according to ethnic group. Although the associations were in the same direction in both groups, the association was only significant in the white subjects (r= - 0.42; P<0.02). The ethnic difference in membrane fluidity was abolished when adjusting for serum triacylglycerols. In conclusion, ethnic differences in erythrocyte membrane fluidity, as determined by the use of TMA-DPH anisotropy, appear to be the result of ethnic differences in the level of serum triacylglycerols.

Urinary acid-base excretion in normotensives and hypertensives of african origin.

Abnormalities in acid-base regulation have previously been reported both in hypertensive humans and animals and a link between abnormalities in renal sodium handling and acid excretion may be particularly important in black hypertensives. The objectives of this study were to compare indices of urinary acid excretion (urinary pH, ammonium and titratable acid excretion) between normotensives and hypertensive people of African origin. Measurements were carried out in 86 black individuals of African origin in a case-control design (19 normotensive; 67 hypertensive). Of these, 17 normotensive and 17 patients with essential hypertension were matched for age, sex and weight. Group comparisons were carried out by unpaired t-tests or two-way analysis of variance and group values are given as means +/- s.d. Urinary pH was significantly higher in the hypertensives both in the unmatched groups and in the matched groups. In the 17 matched pairs: urinary pH in the hypertensive individuals was 6.36 +/- 0.54 and 5.84 +/- 0. 53 in the normotensives, respectively; P = 0.007. Additionally, urinary titratable acidity was significantly lower in the hypertensives than in the normotensives (25.4 +/- 13.7 vs16.7 +/- 10. 7 mmol/24 h; P = 0.047) but there were no significant differences in urinary ammonium excretion. The mechanisms for the apparent reduction in acid excretion in the hypertensives is not clear but these results highlight the possibility that hypertension in blacks is associated with abnormalities of renal sodium and hydrogen exchange with compensatory increases in renal ammonium production.

The mercury sphygmomanometer should be abandoned before it is proscribed.

Both in clinical practice and medical research, blood pressure is still largely measured by auscultation using a mercury sphygmomanometer. Blood pressure is the most important predictor of life expectancy. Treatment of high blood pressure reduces strokes, heart attack and heart failure. Accurate measurement is therefore essential. At a large London teaching hospital, just under 500 mercury sphygmomanometers and their associated cuffs were examined. More than half had serious problems that would have rendered them inaccurate in measuring blood pressure. At the same time, assessment of the technical knowledge needed to measure blood pressure by the ausculatory technique was also carried out amongst medical and nursing staff. This showed a considerable level of ignorance. These results inevitably lead to inaccurate measurement of blood pressure with serious consequences. In addition mercury is a non-degradable pollutant, eventually accumulating on the sea bed. The use of mercury in sphygmomanometers is already in the process of being eliminated in Scandinavia and Holland and other countries are likely to follow. Our results suggest that mercury sphygmomanometers are not adequately maintained and require expertise that is not available for accurate measurement of blood pressure. Their use should be dispensed with on these grounds before a ban for other and, perhaps less justifiable reasons. Validated automatic devices, which are less liable to measurement and observer error should be used instead. At the same time a concerted effort is needed to instruct health care professionals on the importance of more accurate measurement of blood pressure. Journal of Human Hypertension (2000) 14, 31-36.

Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality.

We recently showed that rarefaction of skin capillaries in the dorsum of the fingers of patients with essential hypertension is due to the structural (anatomic) absence of capillaries rather than functional nonperfusion. It is not known whether this rarefaction is primary (ie, antedates the onset of hypertension) or secondary (ie, as a consequence of sustained and prolonged elevation of blood pressure [BP]). The aim of the present investigation was to study skin capillary density in a group of patients with mild borderline hypertension to assess whether rarefaction antedates the onset of sustained elevation of BP. The study group included 18 patients with mild borderline hypertension (mean supine BP, 136/83 mm Hg), 32 normotensive controls (mean BP, 126/77 mm Hg), and 45 patients with established essential hypertension (mean BP, 156/98 mm Hg). The skin of the dorsum of the fingers was examined by intravital capillary videomicroscopy before and after venous congestion at 60 mm Hg for 2 minutes. Patients with borderline essential hypertension had the lowest resting capillary density when compared with normotensive controls and patients with established hypertension. Maximal capillary density with venous congestion in the borderline group remained the lowest. The study confirmed that patients with borderline essential hypertension have skin capillary densities that are equally low as or even lower than patients with established hypertension. Both groups had significantly lower capillary densities than normal controls. One explanation for the results is that capillary rarefaction may be due to an early structural abnormality in essential hypertension.

Maximization of skin capillaries during intravital video-microscopy in essential hypertension: comparison between venous congestion, reactive hyperaemia and core heat load tests.

Intravital capillary video-microscopy is a dynamic method for studying skin capillaries. The technique of direct intravital microscopy (without dyes) depends on the presence of red blood cells inside capillaries for their identification. The aim of the present study was to compare different techniques to try to establish the best method for maximizing the number of visible perfused capillaries during intravital capillary microscopy. We compared the effects of venous congestion with those of post-occlusive reactive hyperaemia (Study 1). We also investigated venous congestion followed first by post-occlusive reactive hyperaemia and then by a core heat load test (Study 2). Finally we investigated venous congestion followed by post-occlusive reactive hyperaemia combined with venous congestion (Study 3). In Study 1, capillary density increased with venous congestion from a baseline value of 74+/-2 (mean+/-S.E.M.) per field to 82+/-3 per field (P<0.0001; analysis of variance). With reactive hyperaemia, there was an apparent decrease in visible capillary density to 69+/-2 per field. In Study 2, baseline capillary density was 69+/-4 per field, and this increased significantly with venous congestion to 74+/-4 per field (P=0.01). With both reactive hyperaemia and core heat load, the apparent density was 62+/-4 per field. In Study 3 the baseline density was 70+/-2 per field, and this increased significantly with venous congestion to 80+/-3 per field (P<0.0001). With reactive hyperaemia combined with venous congestion, the density was 81+/-3 per field (P=0.328 compared with venous congestion alone). The results show that venous congestion at 60 mmHg for 2 min is the most effective method for visualization of the maximal number of perfused skin capillaries during intravital video-microscopy.

Structural skin capillary rarefaction in essential hypertension.

A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension. This rarefaction may play a role in increasing peripheral resistance. However, the mechanism underlying this capillary rarefaction is not understood. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of dorsum of fingers in essential hypertension. The capillary microcirculation was examined with video microscopy before and after maximizing the number of perfused capillaries by venous congestion. The study group comprised 17 patients with essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used intravital video microscopy with an epi-illuminated microscope to examine the skin of the dorsum of left middle phalanx before and after venous congestion at 60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at baseline in hypertensive subjects versus normotensive subjects. With venous occlusion, capillary density increased significantly in both groups; however, maximal capillary density remained significantly lower in the hypertensive subjects than in the normotensive subjects. The study strongly suggests that much of the reduction in capillary density in the hypertensive subjects is caused by structural (anatomic) absence of capillaries rather than functional nonperfusion.

Epithelial sodium channel activity is not increased in hypertension in whites.

Abnormal renal sodium transport causing excess reabsorption of sodium may be one mechanism that causes high blood pressure. For example, increased activity of epithelial sodium channels in the distal tubule is the cause of high blood pressure in Liddle's syndrome, a rare familial form of hypertension. We have shown that the increase in sodium channel activity can be detected in the nose using transepithelial potential difference measurements in 1 family with Liddle's syndrome. We therefore used nasal potential difference measurements to look for increased sodium channel activity in white patients with essential hypertension. Transnasal potential difference was measured in 42 white hypertensive (HT) subjects and 38 white normotensive (NT) subjects before and after topical application of 10(-4) mol/L of amiloride. There was no difference in maximum potential between HT and NT subjects (HT, -18.8+/-0.9 mV; NT, -18.2+/-1.0 mV) (values mean+/-SEM; lumen-negative with respect to the submucosa). However, the postamiloride potential was significantly higher (HT, -12.6+/-0.7 mV; NT, -10.5+/-0.7 mV; P=0. 015) and the change in potential in response to amiloride significantly lower (HT, 6.2+/-0.5 mV, 33.1+/-2.0%; NT, 7.7+/-0.6 mV, 41.9+/-2.0%; P=0.046 and 0.003, respectively) in HT than in NT subjects. These results suggest that sodium channel activity is not increased in whites with essential hypertension and indicate that sodium channel overactivity similar to that seen in Liddle's syndrome is unlikely to be the cause of high blood pressure in this group. Increased postamiloride potential may reflect increased activity of chloride channels or amiloride-insensitive sodium channels.

Importance of the renin system in determining blood pressure fall with salt restriction in black and white hypertensives.

Seventy-one white and 33 black patients with essential hypertension were studied while on a high sodium intake of 350 mmol/d for 5 days and low sodium intake of 10 mmol/d for 5 days. The fall in blood pressure on changing from the high sodium to the low sodium diet was 17/6 mm Hg in whites and 22/10 mm Hg in blacks. Compared with whites, black patients had a 7-mm Hg greater fall (P<0.05) in systolic blood pressure and 4-mm Hg greater fall (P=0.068) in diastolic blood pressure (adjusted for age and blood pressure on the normal diet) with similar changes in urinary sodium excretion. With sodium restriction, plasma renin activity rose from 0.65 to 3.03 ng. mL-1. h-1 in whites, whereas in blacks it rose only from 0.3 to 1.28 ng. mL-1. h-1 (P<0.001 between blacks and whites). From the high to the low salt diet, plasma angiotensin II increased by 31 pmol/L in whites and by 12 pmol/L in blacks (P<0.05 compared with whites), and plasma aldosterone rose by 499 pmol/L in whites and by 256 pmol/L in blacks (P<0.01). Significant inverse correlations were obtained for all patients between the fall in systolic blood pressure from the high to low salt diet and the rise in plasma renin activity and angiotensin II, as well as the absolute level on the low salt diet. These results demonstrate that the larger fall in blood pressure with a reduction in salt intake in blacks is due at least in part to a less responsive renin-angiotensin-aldosterone system in blacks.

Association between atrial natriuretic peptide and cyclic GMP in hypertension and in chronic renal failure.

This study has examined the association between circulating atrial natriuretic peptide (ANP), plasma cyclic GMP and urinary cyclic GMP in relation to hypertension and reduced renal function in 30 normotensives, in 30 patients with essential hypertension and in 22 patients with stable dialysis-independent chronic renal failure (CRF). Plasma ANP was significantly raised (about two-three-fold) in the CRF group compared with the hypertensive and normal groups; plasma cyclic GMP was also significantly raised in the CRF group (median group values: 4.6, 5.8 and 11.0 pmol/ml, respectively, for the normal, hypertensive and CRF groups). There were no significant differences in urinary cyclic GMP between the normotensives and hypertensives but urinary cyclic GMP was significantly reduced in the patients with CRF (median group values: 407.1, 450.9 and 247.8 pmol/min for the normal, hypertensive and CRF groups, respectively, P < 0.001). In the subjects with CRF, the clearance of cyclic GMP was reduced in proportion to the clearance of creatinine, but there was no significant difference in the fractional excretion of cyclic GMP (median group values: 78.1% in the normal group, 78.9% in the hypertensive group and 70.2% in the CRF group). In all groups, there was no association between circulating ANP and urinary cyclic GMP: By contrast, there was a positive association between plasma ANP and plasma cyclic GMP (r = 0.39 P < 0.001) that was independent of blood pressure or renal function. These results demonstrate that while a substantial amount of urinary cyclic GMP originates from the glomerular filtrate, to some extent, raised plasma ANP also contributes to the circulating levels of cyclic GMP. However, plasma cyclic GMP cannot be taken as a direct substitute for plasma ANP.

Association of hypertension with T594M mutation in beta subunit of epithelial sodium channels in black people resident in London.

BACKGROUND: Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation. METHODS: In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive (48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel beta subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing. FINDINGS: 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive participants possessed the T594M variant (odds ratio [OR]=4.17 [95% CI 1.12-18.25], p=0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR=5.52 [1.40-30.61], p=0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median=0.19 ng mL(-1) h(-1)) than in 39 untreated hypertensive individuals without the variant (median=0.45 ng mL(-1) h(-1), p=0.009). INTERPRETATION: Among black London people the T594M sodium-channel beta subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.

Serotonin and heart rate in hypertensive and normotensive subjects.

Plasma and platelet levels of 5-hydroxytryptamine (5 HT) may be altered in essential hypertension. To establish the determinants and correlates of 5 HT in plasma and platelets, we studied 53 untreated subjects with essential hypertension (26 men; 30 whites; mean supine blood pressure 172/101 mm Hg; mean age 49.3 +/- 1.5 years) and 61 normotensive subjects (37 men; 47 whites; mean supine blood pressure 128/78 mm Hg; mean age 42.8 +/- 1.6 years). Plasma and platelet 5 HT were assayed by reverse-phase high performance liquid chromatography with electrochemical detection. No significant difference was found in platelet-poor plasma or platelet 5 HT levels in hypertensive or normotensive subjects (plasma: 43.0 +/- 4.2 and 39.6 +/- 4.4 nmol/L; platelet: 1.65 +/- 1.22 and 1.70 +/- 1.39 nmol/10(9) cells in hypertensive and normotensive subjects, respectively). No significant correlation was found between plasma or platelet 5 HT and systolic or diastolic blood pressure (plasma: r = 0.01 and 0.01 in normotensive subjects and r = 0.01 and -0.14 in hypertensive subjects; platelet: r = 0.12 and 0.13 in normotensive subjects and r = 0.02 and -0.09 in hypertensive subjects). However, plasma 5 HT was associated with supine and standing pulse rates (supine: r = 0.27, p = 0.05 in normotensive subjects and r = 0.54, p < 0.001 in hypertensive subjects; standing: r = 0.19 and r = 0.46, p < 0.001, respectively). Significant relations were also found between platelet 5 HT levels and supine and standing heart rate in the subjects mentioned above (supine: r = 0.28, p = 0.05 in normotensive subjects and r = 0.64, p < 0.001 in hypertensive subjects; standing: r = 0.24 and r = 0.51, p < 0.001, respectively). These associations were stronger in the hypertensive group as a whole, and they held when adjustment was made for differences in age and total blood cholesterol. The present study showed that plasma and platelet 5 HT are not significantly altered in hypertensive subjects. However, plasma and platelet 5 HT levels showed a significant association with supine and standing pulse rate predominantly in hypertensive subjects. This is consistent with experimental evidence of a positive chronotropic effect of 5 HT on perfused hearts and it suggests a possible role of plasma serotonin in the regulation of heart rate.

Contrasting endocrine responses to acute oral compared with intravenous sodium loading in normal humans.

There is evidence in animals and in humans for accelerated natriuresis after oral compared with intravenous sodium loading. To assess the role of atrial natriuretic peptide (ANP) as a contributory mechanism, we compared the hormonal responses to an intravenous sodium load and to the same sodium load taken orally in three separate groups of healthy subjects in balance on low, normal, or high sodium intake. On each diet, there was a trend for an early delay in sodium excretion, followed by increased natriuresis after the oral compared with intravenous sodium load. On all levels of dietary sodium intake, there was a significant (approximately 2-fold) increase in plasma ANP levels after intravenous saline infusion. There was a significant suppression of the renin system both after oral and intravenous sodium loading. However, there was no acute increase in plasma ANP levels after the oral sodium load, except on the very low sodium intake. This striking and unexpected observation suggests that changes in plasma ANP levels appear to play little role in the early response to an acute oral sodium load in subjects with sodium intake in the range of 150-350 mmol/day. Endocrine mechanisms for the accelerated increase in sodium excretion after oral compared with intravenous sodium loading remain to be elucidated.