The purpose of this study was to elucidate the underlying mechanisms of blunted nocturnal blood pressure reduction in non-dipper hypertensive patients. We studied the diurnal variations in systemic hemodynamic indices and baroreflex sensitivity. In 45 subjects with essential hypertension (24 men; mean age, 49+/-1 years), intra-arterial pressure was monitored telemetrically. Non-dippers were defined as those with a nocturnal reduction of systolic blood pressure of less than 10% of daytime systolic blood pressure. Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. Baroreflex sensitivity was calculated as deltapulse interval/deltasystolic blood pressure on spontaneous variations. The mean values of the hemodynamic parameters were calculated every 30 min. Twenty-six subjects were classified as non-dippers. Daytime blood pressure was not significantly different between dippers (149+/-4/87+/-3 mmHg) and non-dippers (147+/-3/82+/-2 mmHg), while the nighttime blood pressure was significantly reduced in dippers (131+/-3/77+/-2 mmHg) but not in non-dippers (145+/-3/80+/-2 mmHg). Nocturnal decreases in both cardiac index and stroke index were smaller in non-dippers (-12.0+/-1.2% and 1.5+/-1.0%) than in dippers (-17.5+/-1.4% and -2.2+/-1.1%). Baroreflex sensitivity significantly increased at nighttime both in dippers (6.5+/-0.6 to 8.0+/-0.7 ms/mmHg) and in non-dippers (5.1+/-0.3 to 6.4+/-0.4 ms/mmHg). Neither daytime nor nighttime baroreflex sensitivity was significantly different between the groups. We conclude that the hemodynamics of non-dipper essential hypertension are characterized by an inadequate nocturnal decrease in cardiac index and stroke index, suggestive of relative volume expansion or malsuppressed sympathetic activity.

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Neurohormonal responses to exercise have not been studied fully in patients with essential hypertension (HT). This study determined if neurohormonal responses to exercise are altered between three subgroups of HT categorized by basal plasma renin activity (PRA). Plasma norepinephrine, epinephrine, atrial natriuretic peptide (ANP), PRA, angiotensin II (All), and aldosterone were measured at rest and after submaximal treadmill exercise in 39 patients with essential HT (WHO classes I–II) and 13 controls. Patients with HT were divided into three subgroups based on the PRA level [low-renin ( < 0.5) HT (n = 14), normal-renin (0.5-2.0) HT (n = 13), and high-renin ( > 2.0) HT (n = 12)]. Patients with HT had higher blood pressure during exercise compared to controls, but blood pressure responses were similar among low-, normal-, and high-renin HT. Neurohormonal factors were comparable between all hypertensives and controls, except for higher plasma All at rest in patients with HT. When neurohormones were compared among three subgroups of HT, plasma norepinephrine and epinephrine responses were similar. Patients with high-renin HT had higher PRA and All, and lower ANP levels at rest and after exercise. In all hypertensives, negative correlations were observed between resting PRA and resting ANP (r = -0.41, p < 0.01), as well as peak PRA and peak ANP (r = -0.33, p < 0.05). Thus, neurohormonal responses to exercise varied with similar cardiac responses among subgroups of essential HT stratified according to renin levels. Patients with high-renin HT had augmented renin-angiotensin system activity with a decrease in ANP levels both at rest and after exercise. A reciprocal relationship between renin-angiotensin system activity and ANP was observed both at rest and after exercise in HT.

The purpose of this study was to elucidate the effects of dietary sodium restriction on diurnal blood pressure (BP) variation in primary aldosteronism. We studied the diurnal variation in the systemic hemodynamic indices and in baroreflex sensitivity (BRS). In 13 subjects with aldosterone-producing adenomas (2 males; mean age, 39+/-2 years), intra-arterial pressure was monitored telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers were defined as those with a nocturnal reduction in systolic BP (SBP) of less than 10% of daytime SBP. Ten subjects showed a non-dipper pattern. Six of these "non-dippers" underwent repetitive hemodynamic studies on the last day of a 1-week low salt diet regimen (NaCl 2-4 g/day). Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. BRS was calculated every 30 min as delta pulse interval/delta SBP on spontaneous variations. Nocturnal reduction of SBP was 4.1% on the normal salt diet. With sodium restriction, urinary sodium excretion decreased from 187+/-8 to 46+/-8 mmol/day, and body weight decreased from 57.9+/-2.1 to 56.6+/-1.9 kg. Night-time BP significantly decreased with dietary modification from 154+/-7/88+/-4 to 140+/-6/78+/-4 mmHg, whereas daytime BP was unaltered. With sodium restriction, cardiac index and stroke index decreased throughout the day. No significant difference was seen in either daytime or nighttime BRS between the two diets. We conclude that the non-dipper pattern is common in patients with an aldosterone-producing adenoma on a normal salt intake, and under such conditions, volume expansion appears to play a major role in the impairment of nocturnal BP reduction.

A 47-year-old Japanese man with mild proteinuria was treated with an ACE inhibitor and antiplatelet agent for 7 years. However, urinary protein levels increased and renal biopsy was performed. Eight out of 20 glomeruli showed global or segmental sclerosis with foamy changes or bubbles, but with a different appearance to typical foam cells or lipoprotein thrombi. "Spike" formation, as observed in membranous nephropathy (MN), was segmentally detected in methenamine silver-stained sections.In an immunofluorescence study, weak linear patterns for IgG and scanty deposits for C3 were observed in glomeruli, but were not specific for immunogenetic MN. An electron microscopy study showed highly dense deposits in the subepithelial, subendothelial, and mesangial areas, in which microbubbles appeared under a higher magnification. Since this case exhibited hypertriglyceridemia and cholesterolemia with high serum apolipoprotein E (apoE) clinically and homozygous apoE2/2 by apoE phenotype and genotype analyses, apoE2 homozygote glomerulopathy was diagnosed and various lipid-lowering agents, e.g., probucol, fenofibrate, and ezetimibe, were administered. However, renal dysfunction gradually developed and peritoneal dialysis was initiated 11 years after the diagnosis. ApoE Toyonaka (Ser197Cys) and homozygous E2/2 were recently identified by direct DNA sequencing. Therefore, non-immune MN-like lesions may develop with the combination of these apoE mutations.