Neuropeptide Y - aspects of vasomotorresponses and receptor characterization

Detta är en avhandling från Medicinska Institutionen Lunds Universitets sjukhus 22185 Lund

Sammanfattning: Abstract The aims of the present thesis were to examine neuropeptide Y (NPY) responses in different human and guinea pig vascular beds and in cultured human vascular smooth muscle cells (VSMC) and to characterize, with different NPY agonists and the specific NPY Y1 receptor antagonist (BIBP3226), the NPY receptors involved. NPY-induced strong and potent contractions in human cerebral and subcutaneous arteries and in guinea pig basilar arteries. The contractions were shown to be mediated solely by the NPY Y1 receptor. In human omental and guinea pig mesenteric arteries, NPY failed to induce contraction, instead a strong, NPY-induced, NPY Y1 receptor-mediated, potentiation of the noradrenaline (NA) -induced contraction was seen. Treatment with antisense oligodeoxynucleotides against the NPY Y1 receptor mRNA abolished the potentiation. The acetylcholine (ACh) -induced dilatation of guinea pig basilar arteries was attenuated by NPY. The receptor involved seemed to be the NPY Y2 receptor. In 50% of the human subcutaneous arteries studied, NPY, apart from contraction, also induced a NPY Y1 receptor-mediated and nitric oxide (NO) dependent vasodilatation. With reverse transcriptase-polymerase chain reaction (RT-PCR) mRNA encoding the human NPY Y1 receptor was detected in human cerebral, subcutaneous and omental arteries and in endothelial cells from human umbilical veins. In cultured VSMC from human subcutaneous arteries, NPY stimulated DNA synthesis and potentiated the NA-induced mitogenesis. Both responses appeared to be induced by the NPY Y1 receptor. Administration of NPY and NA, in-vivo, into the human brachial artery reduced forearm blood flow and increased forearm vascular resistance. The opposite effects were seen after infusion of ATP. The responses were equal in potency and strength in hypertensive and normotensive subjects.

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