The Application of Dynamic Models to the Exploration of <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-4.5269pt" id="M1" height="16.7875pt" version="1.1" viewBox="-0.0657574 -12.2606 16.2376 16.7875" width="16.2376pt"><g transform="matrix(.017,0,0,-0.017,0,0)"><path id="g113-224" d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z"/></g><g transform="matrix(.012,0,0,-0.012,9.541,4.134)"><path id="g50-50" d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z"/></g></svg>-AR Overactivation as a Cause of Heart Failure

<div>The block diagram of conformation changes model. <svg height="12.7178pt" id="M147" style="vertical-align:-3.42947pt" version="1.1" viewbox="-0.0498162 -9.28833 12.3012 12.7178" width="12.3012pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.228,3.132)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g></svg>-AA (I) activates <svg height="12.7178pt" id="M148" style="vertical-align:-3.42947pt" version="1.1" viewbox="-0.0498162 -9.28833 12.3012 12.7178" width="12.3012pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.228,3.132)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g></svg>-AR (<svg height="11.8174pt" id="M149" style="vertical-align:-3.1815pt" version="1.1" viewbox="-0.0498162 -8.6359 12.8231 11.8174" width="12.8231pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M578 512C578 619 494 650 387 650H140L134 622C219 615 223 609 210 542L127 119C112 40 104 34 23 28L17 0H235C317 0 387 7 444 33C515 65 564 122 564 195C564 289 495 335 412 352V354C505 373 578 422 578 512ZM486 510C486 422 423 367 314 367H257L294 565C299 591 305 602 315 608C324 614 339 617 362 617C421 617 486 595 486 510ZM466 200C466 100 393 35 296 35C222 35 198 51 212 127L250 333H303C388 333 466 303 466 200Z" id="g113-67"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.748,3.132)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g></svg>) receptor generating intermediate complexes <svg height="15.2701pt" id="M150" style="vertical-align:-3.834pt" version="1.1" viewbox="-0.0498162 -11.4361 18.408 15.2701" width="18.408pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M578 512C578 619 494 650 387 650H140L134 622C219 615 223 609 210 542L127 119C112 40 104 34 23 28L17 0H235C317 0 387 7 444 33C515 65 564 122 564 195C564 289 495 335 412 352V354C505 373 578 422 578 512ZM486 510C486 422 423 367 314 367H257L294 565C299 591 305 602 315 608C324 614 339 617 362 617C421 617 486 595 486 510ZM466 200C466 100 393 35 296 35C222 35 198 51 212 127L250 333H303C388 333 466 303 466 200Z" id="g113-67"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.813,-5.741)"><path d="M310 541L304 571C290 586 211 619 185 610L80 76L131 52L310 541Z" id="g50-31"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.748,3.784)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g><g transform="matrix(.013,0,0,-0.013,12.694,0)"><path d="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z" id="g113-74"></path></g></svg> with conformation changes. The production of <svg height="15.2701pt" id="M151" style="vertical-align:-3.834pt" version="1.1" viewbox="-0.0498162 -11.4361 18.408 15.2701" width="18.408pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M578 512C578 619 494 650 387 650H140L134 622C219 615 223 609 210 542L127 119C112 40 104 34 23 28L17 0H235C317 0 387 7 444 33C515 65 564 122 564 195C564 289 495 335 412 352V354C505 373 578 422 578 512ZM486 510C486 422 423 367 314 367H257L294 565C299 591 305 602 315 608C324 614 339 617 362 617C421 617 486 595 486 510ZM466 200C466 100 393 35 296 35C222 35 198 51 212 127L250 333H303C388 333 466 303 466 200Z" id="g113-67"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.813,-5.741)"><path d="M310 541L304 571C290 586 211 619 185 610L80 76L131 52L310 541Z" id="g50-31"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.748,3.784)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g><g transform="matrix(.013,0,0,-0.013,12.694,0)"><path d="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z" id="g113-74"></path></g></svg> continues to activate the signal, and then it produces a new substance P and structurally changed receptor <svg height="12.7178pt" id="M152" style="vertical-align:-3.42947pt" version="1.1" viewbox="-0.0498162 -9.28833 12.3012 12.7178" width="12.3012pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.228,3.132)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g></svg>-AR (<svg height="15.2701pt" id="M153" style="vertical-align:-3.834pt" version="1.1" viewbox="-0.0498162 -11.4361 12.8231 15.2701" width="12.8231pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M578 512C578 619 494 650 387 650H140L134 622C219 615 223 609 210 542L127 119C112 40 104 34 23 28L17 0H235C317 0 387 7 444 33C515 65 564 122 564 195C564 289 495 335 412 352V354C505 373 578 422 578 512ZM486 510C486 422 423 367 314 367H257L294 565C299 591 305 602 315 608C324 614 339 617 362 617C421 617 486 595 486 510ZM466 200C466 100 393 35 296 35C222 35 198 51 212 127L250 333H303C388 333 466 303 466 200Z" id="g113-67"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.813,-5.741)"><path d="M310 541L304 571C290 586 211 619 185 610L80 76L131 52L310 541Z" id="g50-31"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.748,3.784)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g></svg>).</div>

Computational and Mathematical Methods in Medicine

fig4

Figure 4

Figure 4: The Application of Dynamic Models to the Exploration of <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-4.5269pt" id="M1" height="16.7875pt" version="1.1" viewBox="-0.0657574 -12.2606 16.2376 16.7875" width="16.2376pt"><g transform="matrix(.017,0,0,-0.017,0,0)"><path id="g113-224" d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z"/></g><g transform="matrix(.012,0,0,-0.012,9.541,4.134)"><path id="g50-50" d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z"/></g></svg>-AR Overactivation as a Cause of Heart Failure 

Computational and Mathematical Methods in Medicine

The Application of Dynamic Models to the Exploration of -AR Overactivation as a Cause of Heart Failure

Figure 4