Pancreatic polypeptide family (APP, BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to α‐adrenoceptor blockade

Abstract

Electrical stimulation of the cat cervical sympathetic trunk caused submandibular salivary secretion and vasoconstriction simultaneously with a contraction of the nictitating membrane. Following a-and /I-adrenoceptor blockade by phentolamine or phenoxybenzamine combined with propranolol, the salivary response and the nictitating membrane contraction upon sympathetic stimulation were almost abolished. A considerable vasoconstrictor response (up to 40% of control) however still remained in the submandibular gland. This yasoconstriction, which persisted after a-adrenoceptor blockade, was rather slow in onset and had a long duration without any poststimulatory hyperemia. Local intra-arterial infusions of noradrenaline caused submandibular vasoconstriction, salivary secretion and nictitating membrane contraction. The blood flow response to exogenous noradrenaline did, however, not mimic the effects of sympathetic nerve stimulation with regard to vascular escape. Whereas the vascular escape after nerve stimulation was followed by a prolonged vasoconstriction with a gradual decline, the escape after noradrenaline infusions was accompanied by a normalization of blood flow. Local intra-arterial infusions of pancreatic polypeptide (PP)-related peptides caused a slowly developing vasoconstriction with a long duration in the submandibular gland, but no salivary secretion or contraction of the nictitating membrane. The relative molar potencies as vasoconstrictory agents were about PYY: 1, neuropeptide Y (NPY):5, avian and bovine pancreatic polypeptid 100. The vasoconstrictor effects of PP-related peptides were resistant to a-adrenoceptor blockade and present also in sympathectomized animals, suggesting a direct action on vascular smooth muscle. Combined local infusions of noradrenaline and NPY caused a vascular response in the submandibular salivary gland which was similar to that seen upon sympathetic nerve stimulation. PYY and NPY caused increase in systemic arterial blood pressure upon systemic administration which indicates general vasoconstrictor actions. This effect was accompanied by a transient bradycardia which was due to inhibition of sympathetic tone, since it was absent in animals treated with propranolol.In conclusion, the present findings illustrate the differential sensitivity to a-adrenoceptor antagonists of the submandibular vasoconstriction and salivation as well as smooth muscle contraction of the nictitating membrane induced by sympathetic nerve stimulation. This remaining vasoconstriction may be explained by release of a nonadrenergic, PP-related transmitter such as NPY which may be present together with noradrenaline in the vascular nerves. Release of an additional vasoconstrictory factor may also account for the finding that infusions of noradrenaline do not mimic the vascular effects of sympathetic nerve stimulation in vivo.

Pheochromocytoma Associated with Nocturnal Hypertension.

“…In this case, NPYconcentration was high not only in the peripheral veins but also in the right adrenal vein, and changes in NPY were roughly parallel to those of NE, indicating that NPYwas co-secreted with NEfrom the tumor. Concerning pressor potency of NPY, previous studies have shown a parallel increase in BP and plasma NPYoccurring in normal subjects (14), and NPYadministration in the intact animal or healthy human induces an elevation ofBP (4,6,15,16). In the present case, although it could not be denied that NPYpotentiated NE-evoked vasoconstriction, the direct contractile effect of NPY, at the levels found, was considered to be negligible.…”

“…Neuropeptide Y (NPY)is a regulatory peptide with a potent vasoconstrictor action, first identified in pig brain (4)(5)(6). It has been reported that NPYis secreted by pheochromocytoma (7,8).…”

Detection of neuropeptide Y and its mRNA in megakaryocytes: enhanced levels in certain autoimmune mice.

“…In addition, NPY-like immunoreactivity has been found in chromaffin cells of the adrenal gland (8). The colocalization of NPY with catecholamines in numerous peripheral and central neurons (2,9), together with its prejunctional inhibitory effects on transmitter release and its vasoconstrictor actions, suggests a function for NPY as a neurotransmitter and/or neuromodulator (2,10). The structure of the NPY precursor has been deduced from a human cDNA clone (11) and from the rat gene (12).…”

Vasoconstrictive action of neuropeptide Y in Bone: The porcine tibia perfused in vivo

“…NE is known to have specificity for alpha, and alpha2 receptors in various organs, including bone (Davis and Wood 1991). Interestingly, the vasoconstriction in cats, elicited by the injection of NPY, has been shown to be resistant to alpha-adrenergic receptor blockade (Lundberg and Tatemoto 1982). It is not known whether the role of NPY in sympathetic neurotransmission in the vascular bed of bone is to potentiate the noradrenergic response by modulating the presynaptic release of norepinephrine or to act directly as a vasoconstrictor.…”