Background: This study investigated the association between arterial stiffness indices and asymptomatic chronic kidney disease (CKD) risk categories in hypertensive patients by using oscillometric device. Methods: Arterial stiffness indices, including 24-hour brachial and aortic systolic blood pressure (SBP) and pulse wave velocity (PWV), were measured by an oscillometric Mobil-O-Graph device, brachial-ankle PWV (baPWV) by a volume-plethysmographic method, and renal resistive index (RI) by ultrasonography, in 184 essential hypertensive patients (66.0 ± 17.1 years, 47.3% male). CKD was categorized into 3 stages based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using a combination of estimated glomerular filtration and albuminuria. Results: The 24-hour aortic PWV (aPWV), baPWV, and RI increased with worsening severity of CKD risk category (all P < 0.01 for trend). Multivariate logistic regression analysis found that a 1 SD increase of nighttime aortic SBP (odds ratio [OR] 1.52), PWV (OR 4.80), or RI (OR 1.75) was an independent predictor of high or very-high CKD stage (all P < 0.05). After adjustment for potential confounders, day-to-night change in brachial SBP as well as in aPWV differed among groups (P < 0.05, respectively). In a multivariate regression model, day-to-night changes in aortic SBP and PWV, and RI were independently associated with day-to-night brachial SBP change. Conclusions: In hypertension, circadian hemodynamics in high CKD stage are characterized by higher nighttime values of aortic SBP and PWV and disturbed intrarenal hemodynamics. Further, the blunted nocturnal BP reduction in these patients might be mediated via disturbed intrarenal hemodynamics and circadian hemodynamic variation in aortic SBP and arterial stiffness.
A 37-year-old man with no past history of hypertension presented with no symptoms but with acutely elevated blood pressure (230/140mmHg) and proteinuria (> 300 mg/dL). Fundoscopic appearance represented grade IV hypertensive retinopathy with papilledema, flamed-shaped hemorrhages, exudates and arteriovenous nipping, indicating typical features of the malignant hypertension. The laboratory tests at admission indicated the possible organ damages in kidney and heart (eGFR 21 mL/min/1.73m2, BNP 263pg/mL). The other examinations are normal. After 20 days of treatments with amlodipine, azilsartan and carvedilol, the average of multiple blood pressure measurements and BNP showed almost normal levels (146/87mmHg, BNP < 10pg/mL), although eGFR level was still under 30. In addition, at this time point, flow mediated dilation (FMD), a noninvasive index of vascular endothelial function measured in forearm, showed significant impairment of endothelial function (%FMD 2.6). At 60 days, fundoscopic images represented entire restoration of retinopathy with disappearance of papilledema, hemorrhage and exudates. In contrast, however, both endothelial and renal function were still under normal levels (%FMD 3.2, eGFR 28.2 mL/min/1.73m2). Notably, FMD showed improvement of sustained endothelial dysfunction at day 90 (% FMD 7.5), while a little recovery of renal function was observed at 360 days (eGFR 35.4 mL/min/1.73m2). This case represents the possibility that damaged endothelial and renal function in acute severe hypertension seem to be still reversal with appropriate anti-hypertensive treatment, while differential time-course recovery in each organ might be existed.
We compared the effects of cilnidipine and nifedipine retard on 24-h blood pressure (BP), heart rate (HR), and autonomic nerve activity in patients with essential hypertension. Cilnidipine is a novel and unique 1,4-dihydropyridine calcium antagonist that has the L-type and N-type voltage-dependent calcium channel-blocking action. Fourteen hypertensive outpatients (four men and 10 women; aged 64 ± 2 years, mean ± SEM) were enrolled in this study. Their ambulatory BP and electrocardiogram were monitored for 24 h at intervals of 30 min with a portable recorder after a 4-week drug-free period, after a 4-week treatment period with cilnidipine (5 or 10 mg once daily), and after a 4-week treatment period with nifedipine retard (10 or 20 mg twice daily). The order of the three periods was randomized. Autonomic nerve activity was evaluated by a power spectral analysis of HR variability, by using the high-frequency (HF) component as an index of parasympathetic nerve activity and the ratio of the low-frequency (LF) component to the HF component (LF/HF) as an index of sympathovagal balance. Cilnidipine and nifedipine retard significantly reduced the 24-h BP of these patients to similar extents (cilnidipine, −11 ± 3/−6 ± 1 mm Hg; nifedipine retard, −15 ± 3/−6 ± 2 mm Hg). Cilnidipine did not change the 24-h average HR, whereas nifedipine retard significantly increased it (+3.3 ± 1.4 beats/min; p < 0.05). Nifedipine retard significantly increased the LF/HF ratio in the daytime and the nighttime. Such changes were limited to the daytime in the treatment period with cilnidipine. These results suggest that cilnidipine is effective as a once-daily antihypertensive agent and had less influence on autonomic nervous system and HR than did nifedipine retard.
Using ryanodine and verapamil. we compared the relative contributions of SR Ca2+ release and gated Ca2+ entry in arterial contractions induced by norepinephrine (NE) between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Aortic rings of 10 SHR and 10 WKY aged 10–12 weeks were superfused in small water-jacketed tissue chambers with physiological salt solution and isometric tension was measured. The inhibition of the NE(3×10-8 M)-induced contraction of aortic rings by ryanodine (10 µM) was significantly greater in WKY (40.1 ± 6.9 %) than in SHR (2.2 ± 9.0 %) (p < 0. 01). The inhibition of the NE-induced contraction by verapamil (10 µM) in the presence or absence of ryanodine (10 µM) was significantly greater in SHR than in WKY. The residual, ryanodine and verapamil-insensitive component of NE-induced contraction was significantly greater in WKY than in SHR. Caffeine(5 mM)-induced contraction in the presence of verapamil and phentolamine was significantly smaller in SHR than in WKY. These results suggest that gated Ca2+ entry plays a more important role in Ca2+ control and that ryanodine-sensitive Ca2+ store is smaller, or the ryanodine receptor is altered in these tissues of SHR compared with those of WKY.
