Dahl Salt-Sensitive Rats Are Protected Against Vascular Defects Related to Diet-Induced Obesity

Abstract

Obesity increases plasma renin activity (PRA) and angiotensin II (ANG II) levels, leading to vascular damage, elevated blood pressure, diabetes, and renal damage. Because genetic deletion of crucial parts of the renin-angiotensin system (RAS) protect against obesity-related cardiovascular defects, we hypothesized that Dahl salt-sensitive (SS) rats, a model of chronically low PRA and ANG II levels, would be protected against vascular defects during diet-induced obesity (DIO) compared to SS.13BN consomic rats showing normal RAS regulation. We evaluated vascular function in middle cerebral arteries (MCA) of SS or SS.13BN rats fed high fat (HF, 45% kCal from fat) vs. normal fat diet (NFD) for 15–20 weeks from weaning. Endothelium-dependent relaxation in response to acetylcholine (ACh 10−8 to 10−4 M) was restored in MCA of HF SS rats vs. NFD controls while vasodilation to ACh was dramatically reduced in HF SS 13BN rats vs. NFD controls. These findings support the hypothesis that physiological levels of ANG II play an important role in maintaining normal vascular relaxation in cerebral arteries and suggest that the cerebral vasculature of the SS rat model is genetically protected against endothelial dysfunction in DIO.

The Renin Angiotensin Aldosterone System and Insulin Resistance in Humans

“…These observational studies make it difficult to determine whether obesity is causing the activated RAS or vice-versa. However, mice with deletions in RAS genes and Dahl salt sensitive rats (a model of low renin and ANGII levels) are protected from diet-induced obesity [ 53, 54 ], suggesting the RAS may have a role in causing obesity and its cardio-metabolic effects, including insulin resistance. Further, insulin resistance is improved with both RAS blockade [ 55 ] and weight loss [ 56 ] in humans.…”

H2S in the Vasculature: Controversy of Mechanisms in Physiology, Pathology and Beyond

“…As the other gasotransmitters NO and CO arguably work in a similar way, the preexisting knowledge of these two ancestors should guide future studies to further the understanding of H 2 S physiology. Human microvessels or rat middle cerebral vessels (MCA) were isolated from fresh tissue and cannulated onto glass pipettes of equal impedance as published previously [72,73]. After preconstriction (human= ET-1; rat= myogenic tone), dilation to increasing amounts of the H 2 S donor NaHS were performed.…”

Obesity-Associated Hypertension

“…This is based on a number of studies showing the development of obesity without concomitant presence of vascular abnormalities (65;72). For instance, mice lacking the Bardet-Biedl syndrome 2 gene do not display endothelial dysfunction despite the presence of obesity (72).…”

“…For instance, mice lacking the Bardet-Biedl syndrome 2 gene do not display endothelial dysfunction despite the presence of obesity (72). More striking is the finding that salt-sensitive (SS) rats fed high fat diet exhibit an improvement in endothelium-dependent vascular relaxation despite the significant weight gain and the presence of several cardiovascular risks including elevated blood pressure and reduced renal function (65). The suppressed RAS appears to account for the improvement in endothelial function in obese SS rats (65).…”

“…More striking is the finding that salt-sensitive (SS) rats fed high fat diet exhibit an improvement in endothelium-dependent vascular relaxation despite the significant weight gain and the presence of several cardiovascular risks including elevated blood pressure and reduced renal function (65). The suppressed RAS appears to account for the improvement in endothelial function in obese SS rats (65). The efficacy of chronic treatment with Ang 1–7, a peptide that negatively modulate RAS activity, in alleviating obesity-associated impairment in endothelium-dependent vasodilation supports further the pathophysiological role of the RAS in obesity-related endothelial dysfunction (73).…”