Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

Abstract

Exercise-induced vessel changes modulate arterial pressure (AP) in male spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short-and long-term exercise training of female SHR and Wistar Kyoto (WKY) rats, 8-9 weeks (200-250 g). Rats were allocated to daily training or remained sedentary for 3 days (N = 23) or 13 weeks (N = 23). After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis) and non-locomotor skeletal muscles (temporalis) were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days) and (SHR = 141%, WKY = 122%, 13 weeks). SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg) that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36%) simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%). In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%), without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time-and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

Effect of gender on training-induced vascular remodeling in SHR

“…Considering only young rats in the hypertensive stage, it was also shown that prolonged exercise protocols caused a greater pressure reduction (39). These results confirmed several previous observations by our group regarding the effectiveness of exercise training in reducing blood pressure in males but not in females (22)(23)(24)(25)(26). Contrary to data reported by Schlüter et al (39), we were also able to show that older SHR trained for up to 3 months may receive some benefits from exercise training, including a small but significant pressure reduction accompanied by a significant reduction of arteriolar wall-to-lumen ratio in locomotor muscles (Caffaro RR, Oliveira RAF, Amaral SL, Baldo MVC, Michelini LC, Rossoni LV, unpublished data).…”

“…In spontaneously hypertensive rats (SHR), the best known experimental model for essential or primary hypertension in humans, we confirmed that high blood pressure levels are accompanied by remodeling of arterioles (increased wall-to-lumen ratio) and capillary rarefaction in many tissues including the skeletal muscles, in which we demonstrated a normal resting blood flow, besides the altered vascular structure (22)(23)(24)(25)(26). According to Mulvany (16), vascular remodeling in hypertension is characterized by increased wall-to-lumen ratio of arteries and arterioles, being classified as eutrophic (decrease in both lumen and outer diameter, with unaltered wall thickness or cross-sectional area) or hypertrophic (increase in media thickening, that encroaches on the lumen).…”

“…Exercise training was not effective in reducing MAP in age-matched female SHR submitted to a similar training protocol (24,26). Interestingly, as observed in Figure 3, in sedentary female SHR hypertension was accompanied by a very strong hypertrophy of the kidney arterioles (wall-tolumen ratio was 2 to 2.5 times greater than that observed in male SHR; compare Figures 3 and 2), but not in the skeletal muscles or heart arterioles that presented a wall-to-lumen ratio in the same range as that of male and female normotensive controls (26).…”

“…In this regard, we have shown that aerobic training increases running performance on a treadmill, measured as attained velocity, time or distance of running in both normotensive and hypertensive male and female rats (24)(25)(26)33,34). Although previous aerobic capacity differs between strains (SHR exhibited a better performance than age-matched WKY normotensive controls) and genders (compared to males, females attained higher velocities during maximal exercise tests on treadmill), we have shown that 3 months of low-intensity aerobic training (50-60% of maximal exercise capacity) induced similar increases in treadmill performance, independent of strain and/or gender (24)(25)(26)33,34).…”

“…There was no hypertrophy to be reversed by training in skeletal muscle or heart arterioles; therefore, training did not change local resistance in exercised tissues of female SHR. As commented above, training was unable to change the wall-to-lumen ratio of non-exercised tissues, and therefore there was no reduction in total peripheral resistance and no pressure fall (24,26). Recently, Schlüter et al (39) published an elegant meta-analysis confirming that sex, age and exercise duration do interfere with the blood pressure response to exercise.…”