The vasoactive effects of bradykinin, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y depend on the perivascular tissue in porcine retinal arterioles in vitro.

PURPOSE: The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail. METHODS: Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue. RESULTS: Bradykinin, VIP and CGRP induced significant concentration-dependent dilatation and NPY significant concentration-dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L-NAME reduced bradykinin- and VIP-induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides. CONCLUSION: The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis.

Crosstalk between cardiomyocyte-rich perivascular tissue and coronary arteries is reduced in the Zucker Diabetic Fatty rat model of type 2 diabetes mellitus.

AIM: We tested the hypothesis that crosstalk between cardiomyocyte-rich perivascular tissue (PVT) and coronary arteries is altered in diabetes. METHODS: We studied the vasoactive effects of PVT in arteries from the Zucker Diabetic Fatty (ZDF) rat model of type 2 diabetes, streptozotocin (STZ)-treated Wistar rats with type 1 diabetes, and corresponding - heterozygous Zucker Lean (ZL) or vehicle-treated Wistar - control rats. Vasocontractile and vasorelaxant functions of coronary septal arteries with and without PVT were investigated using wire myography. RESULTS: After careful removal of PVT, vasoconstriction in response to serotonin and thromboxane analogue U46619 was similar in arteries from ZDF and ZL rats, whereas depolarization-induced vasoconstriction - caused by elevating extracellular [K+ ] - was reduced in arteries from ZDF compared to ZL rats. PVT inhibited serotonin-, U46619- and depolarization-induced vasoconstriction in arteries from ZL rats, but this anticontractile influence of PVT was attenuated in arteries from ZDF rats. Methacholine-induced vasorelaxation was smaller in arteries from ZDF than ZL rats both with and without PVT, and the antirelaxant influence of PVT was comparable between arteries from ZDF and ZL rats. We observed no differences in vasoconstriction, vasorelaxation or PVT-dependent vasoactive effects between arteries from STZ- and vehicle-treated Wistar rats. CONCLUSION: Anticontractile influences of PVT are attenuated in coronary arteries from ZDF rats but unaffected in arteries from STZ-treated rats. Signs of endothelial dysfunction are evident in coronary septal arteries - with and without PVT - from ZDF rats but not STZ-treated rats. We propose that altered signalling between cardiomyocyte-rich PVT and coronary arteries can contribute to cardiovascular complications in type 2 diabetes mellitus.

[Relaxation mechanism of smooth muscle cells and its relationship with penile erection].

The contractile and diastolic function of smooth muscle cells (SMCs) is closely related to penile erection and erectile dysfunction (ED). In addition to nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), sulfur dioxide (SO2), estrogen receptor (ER), P2Y receptor, perivascular tissue (PVT), and calcium activated potassium channel (Kca) are found to be involved in the relaxation of SMCs. This review updates the mechanisms of the relaxation of SMCs and its relationship with ED.

What is the source of anticontractile factor released by the pedicle of human internal thoracic artery?

OBJECTIVES: Perivascular tissue (PVT) surrounding human internal thoracic artery (ITA) releases an unidentified anticontractile factor. The exact source of perivascular tissue-derived relaxing factor (PVRF) is unknown, although the adventitia and adipose tissue have both been suggested as primary candidates, hence the name adventitia or adipocyte-derived relaxing factor (ADRF). To look for the source of ADRF, we examined the dilatory response of human ITA to PVT aliquots in their histological composition. METHODS: We studied isolated ITA segments from 20 patients subjected to coronary artery surgery. The vessels were skeletonized in vitro. ITA rings and PVT were incubated in separate isolated organ baths. The arterial rings were suspended on stainless steel wire hooks in the organ bath chamber. Vessel wall tension was measured with an isometric force transducer. Skeletonized ITA segments were precontracted with 10(-5.5) M phenylephrine. The 5 ml PVT aliquots were next transferred to the ITA tissue bath, resulting in its relaxation. Subsequently, the whole PVT used during experiment was fixed in paraformaldehyde and subjected to histological examination. Tissue was paraffin-embedded, sectioned and stained with haematoxylin and eosin. The paraffin blocks containing PVT were cut into slices every 800 µm to create three-dimensional model. Every PVT specimen was evaluated morphometrically using the Image Pro Plus software to assess the content of three basic kinds of tissues. The ITA relaxation to PVT aliquots was correlated to the histological composition of the PVT. RESULTS: Phenylephrine elicited a 37.82 mN (Q1 = 26.49; Q3 = 46.31) contraction of the ITA. The addition of PVT aliquots to the skeletonized ITA induced a 54.17% (Q1 = 16.73; Q3 = 68.21) relaxation. The median PVT weight was 786 mg (Q1 = 562; Q3 = 976). The PVT composition was as follows: 30.5% (Q1 = 18.5; Q3 = 55.2) adipose tissue, 53.5 (Q1 = 24.6; Q3 = 66.5) muscular tissue and 13.5% (Q1 = 9.9; Q3 = 20.0) connective tissue. This translated into 197.7 mg of adipose tissue (Q1 = 142.2; Q3 = 393.2), 378.9 mg (Q1 = 178.8; Q3 = 537.0) of muscular tissue and 92.4 mg (Q1 = 68.6; Q3 = 185.8) of connective tissue. Neither PVT mass (r = 0.2, P = 0.92) nor adipose tissue (r = -0.2, P = 0.34), muscular tissue (r = 0.3, P = 0.18) or connective tissue (r = -0.2, P = 0.41) content correlated with ITA relaxation response to PVT aliquots. CONCLUSIONS: Adipose tissue from the pedicled ITA graft is an unlikely source of ADRF.

Influence of surrounding tissues on biomechanics of aortic wall.

The present study investigates effects of surrounding tissues and non-uniform wall thickness on the biomechanics of the thoracic aorta. We construct two idealised computational models exemplifying the importance of surrounding tissues and non-uniform wall thickness, namely the uniform-thickness model and the histology image-based model. While the former neglects a connective tissue layer surrounding the aorta, the latter takes it into account with non-uniform wall thickness. Using plane strain finite element analysis, stress distributions in the aortic media between the two models are compared. The histology image-based model substantially enhances the uniformity of stress throughout the aortic media. Furthermore, the altered mechanical properties of surrounding tissues change the stress distribution. These results suggest that surrounding tissues and non-uniform wall thickness should be included in biomechanical analysis to better understand regional adaptation of the aortic wall during normal physiological conditions or pathological conditions such as aortic aneurysms and dissections.