Vasomotor tone is largely maintained by sympathetic nerves, myogenic reactivity and key local and circulating hormones. Acting together, these factors ensure moment-to-moment adjustments of net vascular tone required to maintain hemodynamic stability. In rat mesenteric small veins (MSV) and arteries (MSA), we investigated the contribution of the endothelium, L-type voltage operated calcium channels (L-VOCCs), PKC and Rho kinase to myogenic reactivity. The interaction of myogenic reactivity with norepinephrine (NE), endothelin-1 (ET-1), and sympathetic nerve activation was also investigated under conditions of changing transmural distending pressure. We also evaluated the relative contribution of alpha adrenergic (α-A) and endothelinergic receptors to NE and ET-1 contractile responses, respectively. Additionally, the effects of changing transmural pressure on endothelial dilator function of MSV were examined. Myogenic reactivity was not altered by nitric oxide synthase (NOS) inhibition or endothelium removal in both vessels. L-VOCCs blockade completely abolished arterial tone, while only partially reducing venous tone. PKC and Rho kinase inhibitors largely abolished venous and arterial myogenic reactivity. Increasing transmural pressure did not alter NE, ET-1, and bradykinin responses, but it significantly reduced neurogenic contractions. MSV were more sensitive to NE, ET-1 and sympathetic nerve activation compared with corresponding arteries. α-A and ET-1 receptor agonist and antagonist application revealed the participation of α1-A and ETA receptors in NE and ET-1 contractile responses, respectively. α2-A and ETB receptors appeared to mediate NE and ET-1 responses in MSV, respectively. Bradykinin induced-vasodilation was mainly reduced by NOS inhibition, and BKCa and SkCa blockade. These results suggest that myogenic factors are important contributors to net venous tone in MSV; PKC and Rho kinase activation are important to myogenic reactivity in both vessels, while L-VOCCs play a limited role in the veins versus the arteries; mesenteric veins maintain an enhanced sensitivity to NE, ET-1 and sympathetic nerve activation compared to the arteries with neurogenic contractions being affected by transmural pressure elevations; α1-ARs and ETA are the predominant receptors mediating contractile responses to NE and ET-1, respectively, with functional evidence indicating the presence of α2-ARs and ETB receptors in MSV; and venous endothelial dilator function is not affected by an elevation of transmural pressure. / Natural Sciences and Engineering Research Council of Canada (NSERC). Libyan Ministry of Education and Scientific Research.

Experimental vibration analysis of mechanical structures is a well established field.Plenty of literature exists on macro scale structures in the fields of civil, mechanical and aerospace engineering, but the study of vibrations of micro scale structures such as MEMS, liquid droplets, and biological cells is relatively new. For such structures, the amplitudes of vibration are typically in nanometeror sub-nanometer range and the frequencies are in KHz to MHz range depending upon the dimensions of the structure. In our study, we use a scanningLaser Doppler Vibrometer (LDV) to measure the vibrations of micro-scale objects such as MEMS structures, micro droplets and cells. The vibrometercan capture frequency response up to 24 MHz withpicometer displacement resolution. First, we present the study of dynamics of a 2-D micromechanical structure—a MEMSelectrothermal actuator. The structure is realized using SOI MUMPs process from MEMSCAP. The fabricated device is tested for its dynamic performance characteristics using the LDV. In our experiments, we could capture up to 50 out-of-plane modes of vibration—an unprecedented capture—with a single excitation. Subsequent FEM based numerical simulations confirmed that the captured modes were indeed what the experiments indicated, and the measured frequencies werefound to be within 5% of theoretically predicted. Next, we study the dynamics of a 3-D micro droplet and show how the substrate adhesion modulates the natural frequency of the droplet. Adhesion properties of droplets are decided by the degree of wettability that is generally measured by the contact angle between the substrate and the droplet. In this work, we were able to capture 14 modes of vibration of a mercury droplet on different substrates and measure the correspondingfrequencies experimentally. We verify these frequencies with analytical calculations and find that all the measured frequencies are within 6% of theoretically predicted values. We also show that considering any two pairs of natural frequencies, we can calculate the surface tension and the contact angle, thus providing a new method for measuring adhesion of a droplet on an unknown surface. Lastly, we present a study of vibrations of biological cells.Our first study is that of single muscle fibers taken from drosophila.Muscle fibers with different pathological conditions were held in two structural configurations—asa fixed-fixed beam and a cantilever beam—and their vibration signatures analysed.We found that there was significant reduction in natural frequency of diseased fibers. Among the diseased fibers, we could confidently classify the myopathies into nemaline and cardiac types based on the natural frequency of single fibers. We have noticed that the elastic modulus of the muscle which decides the natural frequency is dictated by the myosin expression levels. Our last example isa study of the vibration signatures of cancer cells. Here we measure the natural frequencies of normal and certain cancerous cells, and show that we can distinguish the two based on their natural frequencies. We find that the natural frequency of cancerous cells is approximately half of that of normal cells. Within the cancerous cells, we are able to distinguished epithelial cancer cells and mesenchymal cancer cells based on their natural frequency values. For Epithelial cells,we activate the signaling pathways to induce EMT and notice the reduction in the natural frequency. This mechanical assay based on vibration response corroborates results from the biochemical assays such as Western blots and PCR, thus opening a new technique of mechano-diagnostics.