Effects of the Rho/Rho-Kinase Pathway on Perfusion Pressure in the Isolated-Perfused Rat Hind Limb Vascular Bed

• Published in: Balkan medical journal 2021-09, Vol.38 (5), p.304-309
• Main Authors: İlhan, Esra, Büyükafşar, Kansu, Tiftik, R Nalan, Seçilmiş, M Ata, Alzayed, Zayed
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Amides - pharmacology; Animals; Atorvastatin - pharmacology; Extremities, Lower; Health aspects; Hemodynamics; Isolation perfusion (Physiology); Leg; Muscle Relaxants, Central - pharmacology; Muscles; Original; Perfusion - methods; Physiological aspects; Protein kinases; Pyridines - pharmacology; Rats; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - metabolism; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - pharmacology
• ISSN: 2146-3123; 2146-3131
• DOI: 10.5152/balkanmedj.2021.20014

Rho/ROCK signaling has been demonstrated to be involved in the vascular reactivity of many arterial networks. However, RhoA expression and the contribution of Rho/ROCK pathway to the control of perfusion pressure have not been investigated in the rat hind limb vascular bed as a skeletal muscle vascular network. To investigate the contribution of the Rho/ROCK pathway in the control of perfusion pressure in the isolated-perfused rat hind limb vascular bed. Animal experimentation. Two Rho inhibitors (atorvastatin and C3 exoenzyme) and ROCK inhibitors (Y-27632 and fasudil) were tested on the phenylephrine-elevated perfusion pressure in the isolated-perfused rat hind limb vascular bed. Furthermore, we sought the expression of RhoA protein in the femoral, popliteal and saphenous arteries as well as quadriceps and gastrocnemius muscles by Western blotting. The ROCK inhibitors Y-27632 and fasudil (both 10-8 to 10-5 M) induced substantial vasodilatations. The maximum vasodilatations induced by Y-27632 and fasudil (both at 10-5 M) were 84.0 ± 6.9% and 76.9 ± 6.9%, respectively (P = .091). Y-27632 was not more potent than fasudil, as the EC50 values for Y-27632 and fasudil were 0.7 ± 2.1 μM and 2.5 ± 2.4 μM, respectively (P = .177). Atorvastatin (10-7 to 10-4 M) and C3 exoenzyme (3 × 10-8 M) also produced vasodilatation (maximum vasodilatation; 20.3 ± 1.7% and 13.7 ± 3.6%, respectively). The EC50 value for atorvastatin was 94.9 ± 1.2 μM. The western blot analysis showed that the femoral, saphenous, and popliteal arteries, as well as the gastrocnemius and quadriceps muscles, express RhoA protein. The Rho/ROCK pathway contributes significantly to the control of perfusion pressure in the rat hind limb vascular bed.