Vessel contractility

Vessel contractility

The experimental use of isolated tissue preparations allows for the study of intact biological structures without interference by external influences such as hormones, autonomic nerves or physical factors.

Resistance arteries are involved in regulating organ-specific blood flow and offer the greatest resistance to blood flowing into tissues.   Studying the effects of test compounds on the vasculature therefore plays an important role in determining the compounds potential effects on blood pressure; ability to cause organ ischaemia; or vascular permeability (leakage) and ensuing oedema.  Hypertension studies tend to focus on resistance vessels because of their ability to change total peripheral resistance.

From our extensive tissue supply network, Biopta can obtain a wide range of organs from which vascular tissues can be obtained. Our scientists are experts in fine dissection procedures, allowing us to isolate functional arteries and veins such as: subcutaneous resistance arteries; mesenteric arteries; coronary arteries; pulmonary arteries; and large muscular or conduit arteries such as aorta, tibial artery or saphenous vein.  The dissection and handling of such tissues without causing damage requires a very high level of operator skill.  Vascular tissue can be secured from both healthy donors and donors with a range of vascular diseases including diabetes, hypertension and atherosclerosis.

Biopta utilise a range of techniques for the study of isolated vascular tissues.  These systems allow the simultaneous measurement of the isometric response to an agonist in a number of vessel sections from one donor:

  • Wire myographs (Danish Myotechnology) are used to study small vessels (diameter of approximately 100 – 1000 µm).  Tissues are mounted between two stainless steel 'jaws' held in place by two ultra-thin wires; as the tissue contracts or relaxes the force is transmitted via one of the wires to a sensitive isometric force transducer, capable of detecting micro-Newton forces (see illustration below).
  • Panlab (Harvard Apparatus) organ baths are typically used to study larger muscular tissues, and are used for the larger conduit arteries such as aorta.  Study of neuronal stimulation of the tissues and the impact of test compound on the resulting contractile response is also possible in this system.

Perfusion myographs (Biopta's patented PM-1 technology) are used to study the responses of intact blood vessels held under physiological pressure or flow conditions.  Changes in vascular permeability can also be assessed in this model; which may indicate how easily a drug can penetrate the vascular wall, or induce a physiological change, such as oedema. 

In many projects, Biopta generate concentration-response datasets, where a test compound is compared to other standard compounds (e.g. competitor's drugs or endogenous hormones or neurostransmitters) in terms of its potency and magnitude of effect in a particular human tissue.

Figure 1: Human subcutanenous arteries show relaxation responses to acetylcholine (ACh) following preconstriction of the arteries with the thromboxane A2 mimetic, U46619. The presence of the test compound, developed to target iNOS, demonstrated side-effects via inibition of eNOS, resulting in reduced relaxation responses to ACh.  The side effect was not observed in the client’s preclinical tests.

 

The concentration dependent effects of serotonin (5-hydroxytryptamine) in human isolated coronary arteries, set up in Biopta's wire myographs, are shown in the graph below. The graph also highlights Biopta's ability to culture blood vessels in order to look at the effect of test compounds over a 2-3 day period.  Human coronary arteries show robust contractile responses to 5-HT after 24 and 48 hours of culture. The location of the concentration effect curve is consistent with historical data from Biopta’s uncultured vessels and now provides us with a protocol to explore the longer term effects of drug treatment on vasoactive pathways; invaluable for exploring both efficacy and safety mechanisms.

Figure 2: Human coronary arteries show robust contractile responses to 5-HT after 24 and 48 hour culture periods.

Biopta's scientists are experts in sourcing, transporting, dissecting and experimenting on isolated tissues and will work closely with you to design a protocol that meets your needs.  Contact us today to discuss studies in isolated tissues or visit our catalogue for industry's widest range of human functional tissue assays.

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