Yuko Tada

Long-term effects of intensive blood-pressure lowering on arterial wall stiffness in hypertensive patients.

BACKGROUND Aortic stiffness is assessed by pulse wave velocity (PWV) and predicts the cardiovascular morbidity and mortality of hypertensive patients. To determine the long-term effects of intensive blood pressure (BP) lowering by antihypertensive drug therapy on aortic stiffness assessed by PWV, a single-blind randomized prospective study was performed. METHODS One hundred forty nondiabetic hypertensive patients (67.6 +/- 0.9 years old; systolic/diastolic BP: 177 +/- 1/101 +/- 1 mm Hg) were assigned to an intensive control group (IC) with a target BP of <130/85 mm Hg (n = 71) or a moderate control group (MC) with a target BP of <140/90 mm Hg (n = 69), and aortic stiffness was assessed every 3 months by measuring aortic PWV with a pulse pressure analyzer. RESULTS During the 12-month treatment period, BP significantly decreased to 129 +/- 1/78 +/- 1 mm Hg and 152 +/- 2/87 +/- 1 mm Hg in the IC and MC, respectively. At the beginning of the study, PWV in the IC and MC was similar, averaging 1779 +/- 41 and 1885 +/- 50 cm/sec, respectively. By the end of the treatment period, however, PWV had decreased to 1621 +/- 34 cm/sec in the IC, but had not changed significantly in the MC. In the IC, the ratio of the change in PWV to the change in BP increased with the duration of BP lowering. Clinical and biological parameters were similar in both groups, except that higher doses of amlodipine were used in the IC. CONCLUSIONS Long-term intensive BP lowering in the hypertensive patients was associated with a significant reduction in aortic stiffness distinct from its acute depressor effect.

Anandamide decreases glomerular filtration rate through predominant vasodilation of efferent arterioles in rat kidneys

For determining the effects of anandamide (ANA) on renal hemodynamics and microcirculation, a clearance study was performed in Sprague-Dawley rats that received injections of ANA in doses of 15, 150, and 1500 pmol/kg. At doses up to 150 pmol/g, ANA significantly decreased GFR and increased renal blood flow (RBF) without affecting mean arterial pressure (MAP). In the presence of the cannabinoid type 1 (CB1) receptor antagonist AM251, only the 15-pmol/kg dose significantly increased GFR and RBF without altering MAP, with higher doses having no effect on GFR, RBF, or MAP. By contrast, AM281, which antagonizes cannabinoid receptors nonselectively, inhibited the GFR, RBF, and MAP responses to ANA. The arteriolar responses to ANA were also assessed in vitro by the blood-perfused juxtamedullary nephron technique. Higher doses of ANA significantly increased the diameter of both afferent and efferent arterioles, whereas lower doses elicited predominant efferent arteriolar dilation. AM251 attenuated the afferent arteriolar response to ANA and inhibited the efferent arteriolar response to ANA, whereas AM281 inhibited the responses in both arterioles. The CB1 receptor mRNA was expressed in afferent arterioles, and immunohistochemical staining demonstrated the presence of CB1 receptors in both afferent and efferent arterioles. These results suggest that ANA causes afferent arteriolar dilation via both CB1 and non-CB1 receptors and greater efferent arteriolar dilation via CB1 receptors, resulting in a decreased GFR and an increased RBF without affecting MAP.

Blunted Tubuloglomerular Feedback by Absence of Angiotensin Type 1A Receptor Involves Neuronal NOS

Abstract—To define the role of angiotensin type 1A (AT1A) receptor in modulating tubuloglomerular feedback signals and to determine its relationship to neuronal NO synthase (nNOS), the diameter of the afferent arterioles of wild-type and AT1A receptor–deficient mice was measured by the blood-perfused juxtamedullary nephron technique. The afferent arteriolar diameter of wild-type and AT1A receptor–deficient mice averaged 16.7±0.6 (n=9) and 16.8±0.7 &mgr;m (n=9), respectively. In the wild-type mice, addition of 10 &mgr;mol/L acetazolamide to the blood perfusate exerted a biphasic afferent arteriolar constriction, with the initial response and sustained response averaging 47.2±3.8% and 33.9±3.3%, respectively. In AT1A receptor–deficient mice, the initial response and sustained response averaged 51.6±3.6% and 9.5±1.3%, respectively, and the sustained response was significantly attenuated compared with that of wild-type mice. Inhibition of nNOS with 10 &mgr;mol/L S-methyl-l-thiocitrulline significantly decreased the afferent arteriolar diameter of AT1A receptor–deficient mice, from 15.1±1.2 to 5.0±0.3 &mgr;m (n=7), and the decrease was significantly greater than that observed in wild-type mice (from 15.9±1.2 to 10.6±1.3 &mgr;m; n=8). During nNOS inhibition, the initial and sustained afferent arteriolar constrictor responses to acetazolamide in wild-type mice averaged 54.4±6.4% and 44.8±11.3%; respectively, and were similar to those in AT1A receptor–deficient mice (53.2±6.4% and 59.5±4.4%, respectively). These results suggest that AT1A receptors enhance tubuloglomerular feedback–mediated afferent arteriolar constriction, at least in part, through reducing the counteracting modulation by nNOS.