Effect of transient receptor potential channel m4 on cerebral artery myogenic tone following subarachnoid hemorrhage in rats / 中国脑血管病杂志

Objective: To investigate the effect of transient receptor potential channel M4 (TRPM4) on cerebral artery myogenic tone following subarachnoid hemorrhage (SAH) in rats. Methods: Sixty cleangrade healthy SD rats of both sexes were randomly divided into SAH group (n = 30) and sham operation group (n =30) according to the random number table. A SAH model was induced by injecting autologous rat tail artery blood into the suprasellar cistern of rats with stereotactic apparatus. 0.2 ml autologous arterial blood was injected into the rats of the SAH group and 0.2 ml isotonic saline was injected into the rats of the sham operation group. Five days after inducing the SAH model,the cerebral arteries of rats were separated, and the diameter of cerebral arteries was observed by the pressurized myography, and the myogenic tone was calculated. The cerebral arteries of each experimental group were observed by time-sequence method for artificial cerebrospinal fluid(aCSF), containing 0. 03 mmol/L TRPM4 specific blocker 9-phenanthrol (9- Phe) aCSF and containing 0. 1 mmol/L diltiazem in the calcium-free aCSF in the arterial diameters, and according to this, the myogenic tone was calculated. Results: After SAH, when the cerebral artery was located in aCSF,the cerebral artery diameter of the SAH group was significantly smaller than that of the sham operation group (45.9 ±6. 6 u.m vs. 74. 9 ±5. 1 u,m,i = 5. 08,P <0. 05). Cerebral artery myogenic tone was significantly higher than that of the sham operation group (58. 7 ±2. 4% vs. 41. 2 ±3. 4%;t - 2.11,P < 0. 05). After adding 9-Phe to aCSF, the diastole of cerebral artery diameters of the SAH group and sham operation group was more obvious than that before adding (98. 4 ± 6. 1 and 95. 1 ±5.5 u,m, respectively). The difference was statistically significant (both P<0.05). The decreased myogenic tone in the SAH group was significantly higher than that in the sham operation group (42. 4 ±4. 4% vs. 15. 3 ± 3. 2%;t =2. 83,P < 0. 05). Conclusion: After SAH,TRPM4 mediates the increased myogenic lone of cerebral artery in rats.

The Role of Reactive Oxygen Species in Pressure-Dependent Myogenic Tone / Jurnal Sains Kesihatan Malaysia

Myogenic tone is the response of the vascular smooth muscle to an increase in intraluminal pressure with vasoconstriction and with vasodilation when the pressure is decreased. Such myogenic tone contributes a level of physiological basal tone in response to neurohumoral stimuli. In spite of myogenic tone discovery by Sir William Bayliss 100 years ago, questions still remain regarding the underlying signaling mechanism of the myogenic response. Studies have shown that increased intraluminal pressure or wall tension leads to membrane depolarization, voltage-operated calcium channel (VOCC), stretch-activated cation (SAC) channels, extracelullar matrix (ECM) and actin cytoskeleton. Recently, evidence has shown a potential role for reactive oxygen species (ROS) as a key signalling mediator in the genesis of myogenic tone. The identification of the primary mechanosensors in the initiation of pressure-dependent myogenic tone is essential as these components could be potential therapeutical targets in the future.

Changes in Myogenic Tone in Spontaneously Hypertensive Rat: Role of RhoA and Protein Kinase C

BACKGROUND AND OBJECTIVES: The myogenic response was originally described as a contraction of a blood vessel that occurred following an increase in intravascular distending pressure. Conversely, a reduction in intravascular pressure produces myogenic vascular relaxation. Recent attention has focused on the potential role of this myogenic mechanism in the control of tone in the resistance vasculature, and in particular on how this mechanism may contribute to the increased vascular resistance seen in hypertension. Therefore, in the present study, we investigated the role of myogenic tone in the generation and/or maintenance of hypertension. MATERICAL AND METHODS: Myogenic tone was developed by stretching of the basilar arteries of WKY (istar Kyoto rat) and SHR (spontaneously hypertensive rats). Contractile responses, PKC (protein kinase C) immunoblots and translocation of PKC and RhoA were measured. In the presence of extracellular Ca2+ the stretching of the resting vessel evoked a myogenic contraction in the basilar arteries of SHR and WKY. Myogenic tone was significantly greater in SHR than in WKY. However, in the absence of extracellular Ca2+, stretching evoked a myogenic contraction in SHR, but not in WKY. The stretch-induced myogenic tone was inhibited by nifedipine. The effect of nifedipine was similar in both SHR and WKY rats. H-7, calphostin C and Y-27632, also inhibited stretch-induced myogenic tone in both SHR and WKY. The inhibitory effects of these drugs were greater in SHR than in WKY. Immunoblotting showed rho A and PKC alpha were translocated from the cytosol to the cell membrane with stretching in both SHR and WKY. PKC beta, however, was translocated to the cell membrane with stretching in SHR, but not in WKY. CONCLUSION: These results suggest that stretch-induced myogenic tone is significantly greater in SHR than in WKY. Furthermore, the increase in amount and/or activity of PKC beta and ROK (rhoA-associated kinase) may be a key mechanism accounting for the enhanced myogenic tone in SHR.

Ca2+ Sensitization Mechanism in Stretch-induced Myogenic Tone

It has been suggested that Ca2+ sensitization mechanisms might contribute to myogenic tone, however, specific mechanisms have not yet been fully identified. Therefore, we investigated the role of protein kinase C (PKC)- or RhoA-induced Ca2+ sensitization in myogenic tone of the rabbit basilar vessel. Myogenic tone was developed by stretch of rabbit basilar artery. Fura-2 Ca2+ signals, contractile responses, PKC immunoblots, translocation of PKC and RhoA, and phosphorylation of myosin light chains were measured. Stretch of the resting vessel evoked a myogenic contraction and an increase in the intracellular Ca2+ concentration ([Ca2+]i) only in the presence of extracellular Ca2+. Stretch evoked greater contraction than high K+ at a given [Ca2+]i. The stretch-induced increase in [Ca2+]i and contractile force were inhibited by treatment of the tissue with nifedipine, a blocker of voltage-dependent Ca2+ channel, but not with gadolinium, a blocker of stretch-activated cation channels. The PKC inhibitors, H-7 and calphostin C, and a RhoA-activated protein kinase (ROK) inhibitor, Y-27632, inhibited the stretch-induced myogenic tone without changing [Ca2+]i. Immunoblotting using isoform-specific antibodies showed the presence of PKCalpha and PKCepsilon in the rabbit basilar artery. PKCalpha, but not PKCepsilon, and RhoA were translocated from the cytosol to the cell membrane by stretch. Phosphorylation of the myosin light chains was increased by stretch and the increased phosphorylation was blocked by treatment of the tissue with H-7 and Y-27632, respectively. Our results are consistent with important roles for PKC and RhoA in the generation of myogenic tone. Furthermore, enhanced phosphorylation of the myosin light chains by activation of PKCalpha and/or RhoA may be key mechanisms for the Ca2+ sensitization associated with myogenic tone in basilar vessels.