Hiroyuki Kinuno

Different platelet aggregability during mental stress in two stages of essential hypertension

To determine whether platelet response to mental stress is altered in essential hypertension, platelet aggregability and plasma beta-thromboglobulin were determined in 24 patients with essential hypertension (11 patients with World Health Organization (WHO) stage I and 13 patients with stage II) and 14 normotensive controls before and after a 10-min arithmetic stress (serial subtraction of 7 from 1000). In normotensive subjects, arithmetic stress did not affect primary aggregations to 1.0 micromol/L adenosine diphosphate (ADP) and to 2.5 micromol/L 5-hydroxytryptamine (5-HT), ADP threshold for biphasic aggregation and plasma beta-thromboglobulin level. In hypertensive patients with WHO stage I, these parameters were similar to those in normotensives before arithmetic stress, but the arithmetic stress test significantly increased primary aggregation to reagents and beta-thromboglobulin level, and decreased threshold of ADP for biphasic aggregation. In WHO stage II patients, platelet aggregability to reagents and beta-thromboglobulin level were already enhanced as compared with WHO stage I patients and normotensive subjects before arithmetic stress. However, the stress-induced changes in platelet function were less pronounced in WHO stage II patients compared with stage I patients. In conclusion, platelet aggregability and proaggregatory effect of mental stress differed depending on the severity of hypertension in patients with essential hypertension; the transient activation of platelet function during stress with no enhancement under the resting condition in the early phase of hypertension and the continuous activation of platelet function in the advanced phase with hypertensive organ damage.

Renal Structural Properties in Prehypertensive Dahl Salt-Sensitive Rats

In 10- to 12-week-old Dahl salt-sensitive (DS) and salt-resistant (DR) rats fed a 0.3% salt diet (n=10 in each group), flow-pressure and pressure-glomerular filtration rate (F-P and P-GFR, respectively) relationships were established for maximally vasodilated perfused kidneys. From these relationships, 3 indices of vascular structural properties were estimated: slope of F-P (minimal renal vascular resistance reflecting overall luminal dimensions of preglomerular and postglomerular vasculature), slope of P-GFR (glomerular filtration capability against pressure), and threshold pressure for beginning filtration at P-GFR (preglomerular-to-postglomerular vascular resistance ratio). Thereafter, maximal renal vascular resistance was determined to assess wall-to-lumen ratios of the resistance vessels in half of each group. In the remainder, the kidneys were perfusion-fixed for histological analysis. Mean arterial pressure did not differ between the DS and DR rats. There were no significant differences in the slopes of F-P between the 2 groups. In contrast, the slope of P-GFR was significantly lower (33%) in DS rats than in DR rats, although the DS kidneys began filtering at a threshold pressure similar to that of the DR kidneys. Thus, in DS rats, there were no abnormalities in luminal dimensions at preglomerular and postglomerular vascular segments, but the kidney filtration capacity decreased at any given increase in pressure. Maximal vascular resistance was greater in DS than in DR rats, a finding compatible with the histological appearance, which showed vascular hypertrophy with little, if any, vascular narrowing in the interlobular arteries of DS rats. In conclusion, hypertrophic remodeling without vascular narrowing at preglomerular resistance vessels and structural defects in filtering at the glomeruli could occur in prehypertensive DS rats.

Blood rheology and platelet function in untreated early-stage essential hypertensives complicated with metabolic syndrome.

We examined whether hemorheology and platelet function are affected in essential hypertensives (EHTs) of the World Health Organization stage I when complicated with metabolic syndrome (Mets). In 156 untreated EHTs, blood viscosity and platelet surface markers were determined. Blood viscosity was significantly elevated in 54 subjects with Mets compared with 102 subjects without Mets. Hematocrit and plasma viscosity increased in the group with Mets, although red blood cell rigidity index “k” did not differ between groups. As a whole group, blood viscosity correlated positively with hematocrit and plasma viscosity. Additionally, plasma viscosity correlated positively with plasma leptin, triglyceride, homeostasis model assessment index, C-reactive protein, and plasma fibrinogen, but negatively with high-density lipoprotein cholesterol. In contrast, no differences were seen in platelet surface markers between groups. In conclusion, EHTs of the early stage complicated with Mets are characterized by increased blood viscosity due to hemoconcentration and increased plasma viscosity.

Effects of uninephrectomy on renal structural properties in spontaneously hypertensive rats

1. To investigate effects of a reduction in nephron numbers on renal structural properties in hypertension, either unilateral nephrectomy (UNX) or sham operation (SO) was performed at 5 weeks of age in spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats (n = 9 for each operation for each strain).

Effects of a novel calcium antagonist, benidipine hydrochloride, on platelet responsiveness to mental stress in patients with essential hypertension.

The effects of a novel calcium antagonist, benidipine hydrochloride, on responses of platelets to mental stress were evaluated in nine patients with essential hypertension. Before and 12 weeks after the monotherapy with benidipine (2-4 mg/day), platelet aggregability and plasma beta-thromboglobulin were determined during rest and after a 10-min arithmetic stress. Before the treatment, arithmetic stress significantly increased platelet aggregability in response to adenosine diphosphate (ADP) and plasma beta-thromboglobulin level. Blood pressure, pulse rate, and plasma catecholamines also increased during arithmetic stress. The treatment with benidipine did not affect resting values of platelet functions, but attenuated significantly stress-induced alterations in primary aggregation to 1.0 microM ADP (34 +/- 4% to 40 +/- 3% before treatment vs. 32 +/- 2% to 34 +/- 3% after benidipine), ADP threshold for biphasic aggregation (2.2 +/- 0.4 to 1.8 +/- 0.3 microM before treatment vs. 2.2 +/- 0.3 to 2.2 +/- 0.4 microM after benidipine) and plasma beta-thromboglobulin level (74 +/- 16 to 104 +/- 15 ng/ml before treatment vs. 60 +/- 10 to 52 +/- 8 ng/ml after benidipine; p < 0.05 for Stress x Treatment interactions in all values). The pretreatment elevations in blood pressure and sympathetic activity with stress were not modified by benidipine treatment. In conclusion, the monotherapy with benidipine did not affect platelet function during the resting condition, but significantly suppressed the platelet activation induced by arithmetic stress in patients with essential hypertension.

Renal vascular structural properties and their alterations by removal of uraemic toxins in a rat model of chronic kidney disease

Renal vascular structural properties and their alterations by removal of uraemic toxins with AST‐120, an oral adsorbent, were examined in subtotal nephrectomized rats. Eight‐ or 9‐week‐old Sprague‐Dawley rats received 3/4 nephrectomy (n = 18) and thereafter were fed 24.5% protein diet with (AST; n = 9) or without (AST–; n = 9) AST‐120 (0.4 g/100 g bodyweight). Sham‐operated rats (Sham; n = 9) received the diet without AST‐120. At 21–22 weeks of age, flow–pressure (F‐P) and pressure–glomerular filtration rate (P‐GFR) relationships were determined for maximally vasodilated, perfused kidneys. The gradient of F‐P (minimal renal vascular resistance reflecting the overall luminal dimensions of pre‐ and post‐glomerular vasculature) was lower in AST– than Sham rats. In contrast, the x‐intercept (preglomerular : post‐glomerular vascular resistance ratio) and gradient (glomerular filtration capacity) of P‐GFR did not differ between the two groups. The vascular wall and lumen at the interlobular arteries were greater in AST– than Sham rats. Although the vascular wall and lumen at the interlobular arteries were less in AST than in AST– rats, the gradient of F‐P and the x‐intercept of P‐GFR did not differ between the two groups. In contrast, the glomerular filtration capacity was greater in AST than AST– rats. In conclusion, the lumen of both pre‐ and post‐glomerular resistance vessels increased and glomerular filtration capacity failed to increase in subtotal nephrectomized rats. Uraemic toxins could play an important role in the development of structural alterations in glomeruli rather than renal resistance vessels in chronic kidney disease.

328 PERSISTENTLY ELEVATED HEART RATE AS A CARDIOVASCULAR RISK IN ESSENTIAL HYPERTENSION: DIFFERENCES ACCORDING TO BLOOD PRESSURE STATUS

Objectives: Persistently elevated heart rate (HR) has been highlighted as a risk of cardiovascular disease. In this study, the association of 24-hour HR with cardiovascular structures was analyzed according to 24-hour blood pressure (BP) status in essential hypertensives (EHT). Design and Methods: In 252 untreated EHT, 24-hour systolic BP (SBP) and HR, glucose and lipid metabolism and neurohumoral factors were measured. Stiffness index “&bgr;” of common carotid artery, a marker of large arterial stiffness was also evaluated by ultrasonic phase-locked echo-tracking system. According to SBP, EHT were divided into three groups: 81 EHT with SBP <130 mmHg (N group), 114 with 130-150 mmHg (M group) and 57 with ≥150 mmHg (S group). Results: In S group, HR positively correlated with cardiovascular risk factors including triglyceride, fasting glucose, homeostasis model assessment ratio, plasma renin activity and plasma norepinephrine (PNE) (r = 0.23, 0.26, 0.23, 0.33, 0.28). Additionally, there was a positive correlation between HR and stiffness index “&bgr;” (r = 0.23). In S group, multiple regression analysis revealed that HR was an independent determinant for stiffness index “&bgr;” in addition to PNE (r2 = 0.08, P <0.05). In contrast, HR did not associate with the cardiovascular risk factors and stiffness index “&bgr;” in either N or M group. Thus, HR could contribute to increase in large arterial stiffness together with elevated sympathetic activity only in EHT with SBP ≥150 mmHg. Conclusions: These data indicate that the cardiovascular effects of persistently elevated HR were different according to BP status in EHT.