Analytical experiments on the mechanism of action of unknown antihypertensive drugs
Ganglion blockers affect the blood pressure drop induced by direct stimulation of the vagus nerve and the boosting effect of clamping the common carotid artery, but do not affect the blood pressure changes induced by acetylcholine and adrenaline, while alpha-blockers reverse only the boosting effect of adrenaline. Certain antihypertensive drugs with specific sites of action (e.g., central or peripheral only) may have blood pressure changes induced by different routes of administration.
Operation method
intravenous injection
Principle
Ganglion blockers affect the blood pressure drop induced by direct stimulation of the vagus nerve and the boosting effect of clamping the common carotid artery, but do not affect the blood pressure changes induced by acetylcholine and adrenaline, while alpha-blockers reverse only the boosting effect of adrenaline. Certain antihypertensive drugs with specific sites of action (e.g., central or peripheral only) may have blood pressure changes induced by different routes of administration.
Materials and Instruments
Cats Move 1. Anesthesia is provided by intravenous injection of 3% sodium pentobarbital (1 ml/kg) at the ear margin. For more product details, please visit Aladdin Scientific website.
Sodium pentobarbital Heparin Hexamethylenediammonium bromide Phentolamine Epinephrine hydrochloride Acetylcholine bromide Saline
Powerlab Instruments Pressure transducers Surgical tables Surgical instruments Tracheal intubation Arterial intubation Arterial clips Static vein intubation Cardiac catheters Syringes Silk threads Yarns
2. a median neck incision was made, the trachea was T-shaped incised, and a tracheal tube was inserted; silk sutures were secured. The purpose of tracheal intubation is to avoid asphyxiation due to excessive airway secretions.
3. Separate the carotid vessels and nerves: the carotid artery, sympathetic nerve, and vagus nerve are wrapped in the same vascular nerve sheath.
(1) Separate the bilateral carotid arteries and thread each separately for backup;
(2) Separate the sympathetic nerve (thin) and vagus nerve (thick) on one side (right side) and thread them separately. Note that the nerves should not be clamped and pulling should be avoided as much as possible.
(1) Cut the vagus nerve at the near-central end of the ligated wire.
② Follow the sympathetic nerve upward and separate it deeply until you find the stellate ganglion (at the angle of the mandible, deeper in location, near the base of the skull, stellate expansion, with multiple branches), and then separate the postganglionic nerves as deep as possible upward. Separate the preganglionic fiber ligation and cut the postganglionic nerve at the near-central end of the ligation line.
Note: The blood supply of the cat is rich and the muscle color is bright red, the operation should be careful, do not cut blindly.
4. Separate the femoral vein for cannulation, the cannula is pre-filled with 0.2% heparin, and the animal is heparinized (1 ml/kg) after completion of femoral vein cannulation. The cannula was secured by silk ligature.
5. The left carotid artery was carefully isolated and cannulated for blood pressure tracing:
(1) The pressure transducer for tracing blood pressure and the connected tubing are pre-filled with heparin and drained of air bubbles. Take care to familiarize yourself with the direction of the tee;
② Arterial clip to clamp the proximal end of the heart;
③ Cut a small opening in the arterial wall (try to cut at the distal end) and insert a cannula that has been pre-filled with heparin; insert more to prevent dislodgement;
④ Release the arterial clip and observe the pulsation of blood in the tube. Note: The height of the pressure transducer should be at the same level as the catheter heart. If necessary, a pre-pressure of 150 mmH2O can be given. silk thread to fix the arterial cannula.
6. The right transient membrane is threaded (at the medial canthus, with the greatest contraction and thickest at the rim) and the tension transducer is attached. Note that the direction should be consistent with the direction of transient membrane contraction.
[Experimental observation
1. Record the normal curve after stabilization: blood pressure, transient membrane contraction.
2. Observation:
(1) Clamp the right carotid artery with an arterial clip for 15 seconds and observe the changes in transient membrane contraction and blood pressure.
(2) Put the pre-sympathetic fibers on the stimulating electrode and stimulate the pre-sympathetic fibers (the sympathetic nerves before the stellate ganglion, which emanate from the thoracolumbar section of the spinal cord and then travel upward) for 10 seconds to observe the changes of the transient membrane contraction and the changes of blood pressure. The stimulation parameters were a 16-Hz square wave with a wave width of 4 ms and an amplitude of 120% of the threshold voltage. The following is the same.
(3) Stimulate the distal end of the post-sympathetic fibers (pull up the ligature) for 10 seconds and observe the changes of transient membrane contraction and blood pressure.
(4) Stimulate the preganglionic fibers of the vagus nerve for 10 seconds and observe the changes in transient membrane contraction and blood pressure.
(5) Administer epinephrine (0.1 ml/kg) intravenously into the femoral vein and observe the changes in transient membrane contraction and blood pressure. Note that when replacing the heparin-filled syringe after administration, gently push a little to inject all the residual drug in the tube into the bloodstream. Same as below.
(6) Acetylcholine (0.1 ml/kg) was injected into the femoral vein, and changes in transient membrane contraction and blood pressure were observed.
3. Two unknown antihypertensive drugs are administered into the femoral vein, drug A and drug B. Drug A is (0.2 ml/kg); drug B is (0.1 ml/kg). After the injection of the unknown antihypertensive drugs, repeat the above observations after the blood pressure drops by 30 mmHg. After the blood pressure dropped by 30 mmHg, the above observations were repeated, i.e., carotid artery clamping; stimulation of pre-sympathetic node; stimulation of post-sympathetic node; stimulation of pre-vagal node; injection of adrenaline into femoral vein; injection of acetylcholine into femoral vein.