In some groups of fat denuded aortic rings, when transfer of ADF- solution, it shows an increase of vessel excitation and tonic contraction with rhythmic and spike activity.
This phenomenon can last for more than 40 minutes and return to normal after washout of the ADF- solution (figure 34).
Figure 34 :
Effect of resting tension after transfer of ADF-solution, a rise up of baseline with vessel excitation and tonic contraction.. This phenomenon can last for more than 40 minutes. The baseline return to normal level after the ADF-solution has been washed out ADF-solution: fat solution containing adipose derived factor.Chapter 4
Discussion:
It is well known that the fat tissue plays may different functions on our body. Obesity, manifest itself as a high body mass index (BMI), defined as the fat tissue accumulated much more than the normal.(82) Obesity is associated with a major pathological change in human, the so called metabolic syndrome. It includes high blood pressure.
In prior studies, investigators reported the perivascular adipose tissue (PVAT) plays a vascular relaxation function due to the release a factor “adipoose derived relaxing factor” (ADRF) (76,77,78) Means if more adipose tissue surrounding the vessels will cause more relaxation to the vessels. Under this circumstance, people who are obese will have lower blood pressure than the non-obese one. It is clearly different from the clinical findings which indicate that obese people tend to have higher blood pressure. . We assume that the PVAT has some functions which can influence the blood vessel tone, can enhance vascular contraction instead of relaxation. We used the rat thoracic aortic rings, with either fat intact (F+) aortic rings, fat denuded (F-) aortic rings or F- aortic rings but with an extra transfer fat solution which stimulated by PE, KCl, Ang.II or relaxed by CCh. Our novel finding demonstrated that PVAT caused a significant enhance in sensitivity to PE and KCl and so increase vascular contractile response in either F+ aortic rings, F- aortic rings exposed to solution incubated with fat solution compared to F- aortic rings. Or in some groups of F- aortic rings exposed to fat solution they showed an elevation of resting tension soon after transferring fat solution to the F- aortic rings even in the absence of stimulant without PE or KCl, i.e.
it changed the resting tension. They appeared with a vessel excitation and tonic contraction. This phenomenon can last for more than 40 minutes and returned to the baseline till the solution has been thorough washout. When those F- aortic rings had add with PE and up to an optimal level, we used CCh to test the endothelial-dependent relaxing function, it showed a good relaxation response. But when we transfer the fat solution to the F- aortic rings before reacted with PE, it showed an
that the PVAT can release a factor, so called “Adipose derived factor” (ADF) to cause elevated vascular tone, where the contractile response is proportional to the fatty mass. That means, the more concentration of F solution, the more vessel contractile response. These experimental results were different to the reported earlier.
In those groups of F+ aortic rings, F-aortic rings with transfer fat solution (ADF), they all showed an enhance sensitive as elevated contractile response at low concentration of PE and KCl as compared to the F-aortic rings. In those rings after the transfer ADF to the F- aortic rings after stimulated with PE and KCl, an enhance contractile response to the vessel was also observed. However, in those groups of F+
aortic rings, after PE or KCl were washout, they usually shown a transit contraction and a slow relaxation
(a long half time of maximal relaxation). This phenomenon were not seen in those F- aortic rings or F- aortic ring with incubation of ADF, so it is possible to explain that the transient contraction and slow relaxation is due to the fatty barriers, causing a delay washout response to PE and KCl.
We used different methods to test the characters of PVAT. Matthias Lohn et al (77) reported that transfer of fat solution to the F- aortic rings, greatly eliminated the contractile response and dose response-relationship to incremental doses of Ang.II over a wide range ( from 1 to 300 nM). We used Ang.II at the concentration 100, 200 or 375 nM to test whether the ADF has a vaso-dilate response or not. We transfer ADF to F- aortic rings and found that transfer of ADF to the F- aortic rings either before or after stimulation by Ang.II. None of them showed vaso-dilating effect.
Some of them even showed an increase contractile response as compared to the control groups. We were not able to construct a dose-response curve in the same aortic rings. It is because the phenomenon of tachyphylaxis (83,84), It is suggested that tachyphylaxis depends on a slowly reversible alteration of a calcium translocation step in the stimulus-response coupling. This can diminished response to later increments in a sequence of activation by Ang.II to the vessels (85). Gao et al (80) found that PVAT caused an increase in electrically stimulated vascular contractile response in mesenteric artery due to the formation of superoxide, and the contractile response can be diminished by superoxide dismutase (SOD). We used PE,
following the transfer of F-solution. The enhanced vascular contraction in this groups is apparently due to a diffusible factor (or factors) released from the fat tissue.
To determine whether the ADF is a kind of heat sensitivity or not. We first boiled the fat solution (ADF) up to 100 C, then cooled down to the room temperature, and transferred to the F- aortic rings. The boiled ADF did not show an significant enhance sensitive to PE or KCl that increase vascular contraction in the F – aortic rings. We consider that ADF may be a heat sensitive protein or peptide, which can be de-natured by heat and thus loss its function (86,87).
Conclusion: According to our experiments, we can know that the fat tissue can release a factor ”adipose derived factor” that play a vessel contractile effect. Although the real mechanism is still unknown, it is quite consistent that in obese people who have a high percentage of high blood pressure or vascular disease than those who are non obese. It give us a further new concept to understand the relationship between obesity and systemic disease. The physiological significance of perivascular fat is at best speculatory and requires more rigid future investigation
.
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