Low-Intensity Voluntary Running Lowers Blood Pressure with Simultaneous Improvement in Endothelium-Dependent Vasodilatation and Insulin Sensitivity in Aged Spontaneously Hypertensive Rats

Exercise training lowers blood pressure and is a recommended nonpharmacological strategy and useful adjunctive therapy for hypertensive patients. Studies demonstrate that physical activity attenuates progression of hypertension. However, underlying mechanisms remain elusive. Vascular insulin resistance and endothelial dysfunction plays a critical role in the development of hypertension. The present study investigated whether long-term physical exercise starting during the prehypertensive period prevents the development of hypertension via improving vascular insulin sensitivity. Young (4 wk old) prehypertensive spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) control rats were subjected to a 10-wk free-of-loading swim training session (60 min/day, 5 days/wk). Blood pressure, mesenteric arteriolar vasorelaxation, G protein-coupled receptor kinase-2 (GRK2) expression and activity, and insulin-stimulated Akt/endothelial nitric oxide synthase (eNOS) activation were determined. SHRs had higher systolic blood pressure, systemic insulin resistance, and impaired vasodilator actions of insulin in resistance vessels when compared with WKY rats. Systolic blood pressure in SHRs postexercise was significantly lower than that in sedentary rats. Vascular insulin sensitivity in mesenteric arteries was improved after exercise training as evidenced by an increased vasodilator response to insulin. In addition, exercise downregulated vascular GRK2 expression and activity, which further increased insulin-stimulated vascular Akt/eNOS activation in exercised SHRs. Specific small interfering RNA knockdown of GRK2 in endothelium mimicked the effect of exercise-enhanced vascular insulin sensitivity. Likewise, upregulation of GRK2 by Chariot-mediated delivery opposed exercise-induced vascular insulin sensitization. Taken together, our results suggest that long-term exercise beginning at the prehypertensive stage improves vascular insulin sensitivity via downregulation of vascular GRK2 that may help to limit the progression of hypertension.

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Insulin sensitivity and hemodynamic responses to insulin in Wistar-Kyoto and spontaneously hypertensive rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.271.4.e658 ◽

1996 ◽

Vol 271 (4) ◽

pp. E658-E668 ◽

Cited By ~ 9

Author(s):

M. Pitre ◽

A. Nadeau ◽

H. Bachelard

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Insulin Sensitivity ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Hemodynamic Responses ◽

Spontaneously Hypertensive ◽

Wky Rats ◽

Vascular Beds ◽

Wistar Kyoto

The insulin-mediated vasodilator effect has been proposed as an important physiological determinant of insulin action on glucose disposal in normotensive humans. The present study was designed to further examine the acute regional hemodynamic effects of insulin in different vascular beds and to explore the relationships between insulin vascular effects and insulin sensitivity during euglycemic hyperinsulinemic clamps in conscious normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and regional blood flows. In WKY rats, the euglycemic infusion of insulin (4 and 16 mU.kg-1.min-1) causes vasodilations in renal and hindquarter vascular beds but no changes in mean blood pressure, heart rate, or superior mesenteric vascular conductance. In contrast, in SHR, the same doses of insulin produce vasoconstrictions in superior mesenteric and hindquarter vascular beds and, at high doses, increase blood pressure. Moreover, at the lower dose of insulin tested, we found a reduction in the insulin sensitivity index in the SHR compared with the WKY rats. The present findings provide further evidence for an association between insulin sensitivity and insulin-mediated hemodynamic responses.

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Consequences of low-intensity light at night on cardiovascular and metabolic parameters in spontaneously hypertensive rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0043 ◽

2019 ◽

Vol 97 (9) ◽

pp. 863-871 ◽

Cited By ~ 5

Author(s):

Valentina Sophia Rumanova ◽

Monika Okuliarova ◽

Lubos Molcan ◽

Hana Sutovska ◽

Michal Zeman

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Systolic Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Metabolic Parameters ◽

Adult Males ◽

Hypertensive Rats ◽

Light At Night ◽

Spontaneously Hypertensive ◽

Low Intensity

Circadian rhythms are an inherent property of physiological processes and can be disturbed by irregular environmental cycles, including artificial light at night (ALAN). Circadian disruption may contribute to many pathologies, such as hypertension, obesity, and type 2 diabetes, but the underlying mechanisms are not understood. Our study investigated the consequences of ALAN on cardiovascular and metabolic parameters in spontaneously hypertensive rats, which represent an animal model of essential hypertension and insulin resistance. Adult males were exposed to a 12 h light − 12 h dark cycle and the ALAN group experienced dim light at night (1–2 lx), either for 2 or 5 weeks. Rats on ALAN showed a loss of light–dark variability for systolic blood pressure, but not for heart rate. Moreover, a gradual increase of systolic blood pressure was recorded over 5 weeks of ALAN. Exposure to ALAN increased plasma insulin and hepatic triglyceride levels. An increased expression of metabolic transcription factors, Pparα and Pparγ, in the epididymal fat and a decreased expression of Glut4 in the heart was found in the ALAN group. Our results demonstrate that low-intensity ALAN can disturb blood pressure control and augment insulin resistance in spontaneously hypertensive rats, and may represent a serious risk factor for cardiometabolic diseases.

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