The effect of renal perfusion pressure on renal vascular resistance in the spontaneously hypertensive rat

Renal hemodynamics and renal vascular resistance (RVR) were measured in the spontaneously hypertensive rat (SHR) and in the normotensive Wistar-Kyoto rat (WKY). In addition, the autoregulatory response and segmental RVR in the SHR were studied after aortic constriction. Mean arterial pressure (MAP) and RVR were higher in the SHR than in the WKY, but renal blood flow (RBF) and glomerular filtration rate were similar in both groups. Measurement of mean afferent arteriolar diameter (AAD) by a microsphere method showed a significantly smaller AAD in SHR (17.7±0.35 μm) than in the WKY (19.5±0.20 μm). This decrease in AAD could account for a 47% increase in preglomerular resistance. Aortic constriction in the SHR, sufficient to reduce renal perfusion pressure from 152 to 115 mm Hg, did not alter the AAD. Since RBF and glomerular filtration were also well maintained following aortic constriction, these autoregulatory responses suggest that vessels proximal to the afferent arteriole rather than postglomerular vasculature are primarily involved in the changes on intrarenal vascular resistance in SHR.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47448/1/424_2004_Article_BF00581421.pd

Randomized, double-blind, placebo-controlled, clinical study on the effect of Diabetinol® on glycemic control of subjects with impaired fasting glucose

Malkanthi Evans,1 William V Judy,2 Dale Wilson,3 John A Rumberger,4 Najla Guthrie,1 1KGK Synergize Inc., London, ON, Canada; 2SIBR Research Inc., Bradenton, FL, USA; 3London Health Sciences Center, University of Western Ontario, London, ON, Canada; 4Princeton Longevity Center, Princeton, NJ, USA Background: This study investigated the efficacy of Diabetinol® in people with diabetes on medication but not meeting the American Association of Clinical Endocrinologists and American Diabetes Association glycemic, blood pressure, and lipid targets. Subjects and methods: Fifty subjects, aged 18–75 years, with fasting blood glucose ≤15.4 mmol/L, hemoglobin A1c levels ≤12%, and a body mass index between 25 and 40 kg/m2, were enrolled in a 24-week, randomized, double-blind, placebo-controlled, parallel study. Diabetinol® or placebo was administered as 2×525 mg capsules/day. Results: In the Diabetinol® group, 14.3% versus 0% in the placebo group, 33.3% versus 15.4% in placebo, 20.0% versus 12.5% in placebo, and 83.3% versus 60% in placebo achieved the American Association of Clinical Endocrinologists and American Diabetes Association targets for hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic blood pressure, respectively. There was no difference in the maximum concentration (Cmax) of serum glucose or area under the curve (AUC)0–240 minutes. The time to Cmax was longer for participants on Diabetinol® than placebo group at week 12 (P=0.01). Fasting blood glucose increased from baseline to week 24 in both groups; however, this increase was 14.3 mg/dL lower in the Diabetinol® group versus placebo. The Diabetinol® group showed an increase of 5.53 mg/dL in fasting insulin at week 12 (P=0.09) and 3.2 mg/dL at week 24 (P=0.41) over and above the placebo group. A decrease of 1.5% in total cholesterol, 5.8% in low-density lipoprotein, and a 1.6% increase in high-density lipoprotein concentrations were seen in the Diabetinol® group. Diabetinol® improved 6-month oral glucose tolerance test and 2-hour postprandial glucose profiles in participants between 40 and 60 years of age. Conclusion: The current study suggests a role for Diabetinol® as an adjunctive therapy for glycemic maintenance and for decreasing the risk of diabetes-associated comorbidities in type 2 diabetic patients on conventional therapies. Keywords: diabetes, insulin, citrus flavonoids, limonoids, hyperlipidemia, hypercholesterolemia, adjunctive therap