Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage.

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.

Racial differences in renal vascular response to angiotensin blockade with captopril or candesartan.

OBJECTIVE: We compared the renal vascular response to captopril and candesartan among nondiabetic, normotensive black and white participants to explore angiotensin-converting enzyme-independent generation of angiotensin II. METHODS: Thirteen black individuals and 10 white individuals in low-salt balance were given captopril and candesartan on sequential study days, and the renal plasma flow responses to these agents were measured. RESULTS: Consistent with our prior observations, white individuals demonstrated a strong, significant correlation between responses to these drugs (r = 0.78, P = 0.008) and a significantly greater increase in the renal plasma flow in response to candesartan compared with captopril (104.2 +/- 26.8 versus 52.4 +/- 24.3 ml/min per 1.73 m; P = 0.03). In black participants, however, no correlation between responses to captopril and to candesartan was observed (r = 0.22, P = 0.47) and there was no difference in the renal plasma flow response between the two drugs (90.4 +/- 13.0 versus 80.4 +/- 15.3 ml/min per 1.73 m; P = 0.59). The difference in the response to the two drugs was significantly higher among white participants compared with black participants (P = 0.03). CONCLUSION: We confirmed the contribution of an angiotensin-converting enzyme-independent pathway for angiotensin II generation in the kidneys of nondiabetic, normotensive white, but not black, individuals.

Renin release in response to Renin system blockade: activation of the Renin system in type 1 diabetes mellitus.

Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade. Forty-four consecutively enrolled Type 1 diabetic patients (28.2+/-1.5 years) and 37 normal subjects (37+/-2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan. As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6+/-1 ng/mL Ang I/hour in diabetic patients, and 1.7+/-0.9 ng/mL Ang I/hour in normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1+/-17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2+/-13.9 ml/minute/1.73 m2; p=0.006). Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients.