Effect of endothelin-1 on regional vascular resistances in the pig.

The actions of endothelin-1 (ET-1) on vascular resistances were investigated and characterized in anesthetized pigs in vivo. Intravenously administered ET-1 (2-400 pmol/kg) caused dose-dependent increases in mean arterial blood pressure accompanied by a reduction in heart rate. ET-1 also increased renal, coronary, femoral, and bronchial vascular resistances.

Involvement of neuropeptide Y in sympathetic vascular control of skeletal muscle in vivo.

The possibility that neuropeptide Y, a vasoconstrictor peptide co-stored with noradrenaline in sympathetic nerves, participates in neurogenic vascular control was investigated in canine gracilis muscle in situ. Sympathetic nerve stimulation with recordings of the normal irregular sympathetic discharge to human skeletal muscle elicited frequency-dependent overflows of neuropeptide Y-like immunoreactivity and noradrenaline, and vasoconstriction. The overflow of neuropeptide Y-like immunoreactivity was more markedly enhanced with increasing frequency.

Noradrenaline release evoked by a physiological irregular sympathetic discharge pattern is modulated by prejunctional alpha- and beta-adrenoceptors in vivo.

1. Sympathetic nerve stimulation-evoked overflow of endogenous noradrenaline (NA) and vasoconstriction were studied in canine blood-perfused gracilis muscle in situ. Nerves were stimulated at an average frequency of 2 Hz (240 pulses, 120 s) with impulses derived from a recording of the normal irregular sympathetic discharge to human skeletal muscle, with regular bursts of impulses, or with the conventional continuous stimulus mode.

Effects of neuropeptide Y, calcitonin gene-related peptide, substance P, and capsaicin on cerebral arteries in man and animals.

The smooth-muscle tone of pial, middle, and anterior cerebral arteries from humans, cats, and pigs, respectively, was studied in vitro with respect to the effects of capsaicin and various peptides which are present in local perivascular nerves. Neuropeptide Y (NPY) caused concentration-dependent, potent contractions of the cerebral vessels both in the presence and in the absence of endothelium. In contrast to the response to noradrenaline (NA) and K+, the NPY effect was not altered by changes in the extracellular Ca++ concentration.

Renal sympathetic nerve activation in relation to reserpine-induced depletion of neuropeptide Y in the kidney of the rat.

The effect of reserpine treatment on renal sympathetic nerve activity and tissue levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) were studied in rats. Injection of reserpine (1 mg kg-1 i.v.

Neuropeptide Y and reserpine-resistant vasoconstriction evoked by sympathetic nerve stimulation in the dog skeletal muscle.

1. The effects of sympathetic nerve stimulation (evoked by recordings of authentic irregular vasoconstrictor nerve fibre discharge with average frequencies of 0.59, 2.

Baroreflex modulation of sympathetic activity and sympathetic neurotransmitters in humans.

We raised and lowered arterial pressures with stepwise intravenous infusions of phenylephrine and nitroprusside in ten healthy young men and measured changes of R-R intervals, post-ganglionic peroneal nerve muscle sympathetic activity, and antecubital vein plasma noradrenaline and neuropeptide Y concentrations. Respiratory peak-valley R-R interval changes declined with arterial pressure reductions, but did not rise with pressure elevations. Sympathetic activity was modulated by respiration over the entire range of pressures and, at each pressure, was more prominent in expiration than inspiration.

Co-release and functional interactions of neuropeptide Y and noradrenaline in peripheral sympathetic vascular control.

1. The immunohistochemical results suggest that NPY-LI co-exists with NA in sympathetic periarterial nerves of skeletal muscle. The corresponding veins are associated with few or no sympathetic nerves.

Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle.

Sympathetic nerve stimulation (2 min, 2 and 10 Hz) increased perfusion pressure in the blood perfused canine gracilis muscle in situ after pretreatment with atropine, desipramine and beta-adrenoceptor antagonists. This vasoconstriction was accompanied by clear-cut increases in the overflow of endogenous noradrenaline (NA) at both frequencies and, at 10 Hz but not at 2 Hz, also of neuropeptide Y-like immunoreactivity (NPY-LI). The irreversible alpha-adrenoceptor antagonist phenoxybenzamine enhanced the nerve stimulation induced overflows of NA and NPY-LI five- to eightfold and threefold, respectively.

Alpha-adrenoceptor influence on plasma levels of neuropeptide Y-like immunoreactivity and catecholamines during rest and sympathoadrenal activation in humans.

Antecubital venous plasma neuropeptide Y-like immunoreactivity (NPY-LI) and catecholamines were analyzed in six healthy volunteers performing a graded bicycle exercise without medication and after acute administration of clonidine, phentolamine, and nifedipine. During the control exercise, plasma noradrenaline (NA), adrenaline (A), and NPY-LI increased to 17-, 7-, and 3-fold the resting values, respectively, at a maximal workload. Clonidine (300 micrograms p.

Neuropeptide Y: presence in perivascular noradrenergic neurons and vasoconstrictor effects on skeletal muscle blood vessels in experimental animals and man.

The presence of neuropeptide Y (NPY)-like immunoreactivity (-LI) in sympathetic perivascular nerves and the functional effects of NPY and noradrenaline (NA) on vascular tone were studied in skeletal muscle of various species. A dense network of NPY-LI was found around arteries and arterioles but not venules in the gluteus maximus muscle of man, gracilis muscle of dog, tenuissimus muscle of rabbit and quadriceps muscle of cat, rat, guinea pig and pig. The distribution of NPY-immunoreactive (-IR) nerves was closely correlated to the presence of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH)-positive fibers, two markers for noradrenergic neurons.

Neuropeptide Y and noradrenaline mechanisms in relation to reserpine induced impairment of sympathetic neurotransmission in the cat spleen.

The mechanisms underlying the reserpine-induced impairment of the functional responses to sympathetic nerve stimulation and output of noradrenaline (NA) and neuropeptide Y (NPY)-like immunoreactivity (-LI) were studied using the isolated blood-perfused cat spleen. Splenic nerve stimulation (10 Hz for 2 min) during control conditions caused perfusion-pressure increase, volume reduction and an increased output of NA and NPY-LI. After administration of phenoxybenzamine, the nerve stimulation-induced perfusion-pressure increase was almost abolished, the volume reduction inhibited and the output of NPY-LI enhanced.

Actions of calcium antagonists on pre- and postjunctional effects of neuropeptide Y on human peripheral blood vessels in vitro.

The mechanisms underlying the contractile effects of neuropeptide Y (NPY) in relation to those of noradrenaline (NA) on small human blood vessels were studied in vitro. NPY caused contractions of mesenteric veins, renal and skeletal muscle arteries but not of mesenteric arteries. NPY was about 5- to 10-fold more potent than NA.

Cardiovascular effects of calcitonin gene-related peptides I and II in man.

Calcitonin gene-related peptide (CGRP) is present in sensory nerve fibers in the heart and around peripheral arteries. On interaction with specific CGRP binding sites and activation of adenylate cyclase, CGRP causes vasodilation and has positive inotropic and chronotropic effects on the heart. In the present study, human CGRP I and II exerted positive inotropic effects on isolated human right auricles and relaxed small arteries from human skeletal muscle precontracted with norepinephrine (EC50 for CGRP I 0.

Vasoconstrictor effects in vivo and plasma disappearance rate of neuropeptide Y in man.

Vascular effects of neuropeptide Y (NPY) and noradrenaline (NA) were studied in six human volunteers. Systemic infusion of human NPY for 40 min (5 pmol X kg-1 X min-1) increased arterial plasma NPY-like immunoreactivity (NPY-LI) from 12 +/- 2 to 356 +/- 30 pM. This concentration caused no systemic cardiovascular effects.

Effects of antihypertensive drugs on sympathetic vascular control in relation to neuropeptide Y.

The present paper summarizes some recent studies supporting that neuropeptide Y (NPY) is involved as a cotransmitter or modulator with catecholamines (CA) in peripheral, sympathetic, and cardiovascular control, and that many drugs used for the studies or treatment of hypertensive disorders influence NPY mechanisms both at the pre- and postjunctional levels. Neuropeptide Y is stored in large dense-cored vesicles and coreleased with noradrenaline (NA) from postganglionic, sympathetic nerves, and with adrenaline (ADR) from the adrenal medulla. Neuropeptide Y release occurs mainly upon high stimulation frequencies or during strong sympathetic reflex activation in animals and humans.

Plasma neuropeptide Y-like immunoreactivity and catecholamines during various degrees of sympathetic activation in man.

Neuropeptide Y-like immunoreactivity (NPY-LI) and catecholamine concentrations in plasma were analysed during and after 60 min of physical exercise at a work load corresponding to 70% of individual maximal oxygen uptake in nine healthy men of average physical fitness. Systemic plasma NPY-LI increased progressively from 18 +/- 3 to 81 +/- 19 pmol X 1(-1) in parallel with a 10-fold increase in noradrenaline (NA) concentration. The increase in plasma NPY-LI during exercise and the decrease after completion of exercise were much slower than the corresponding changes in NA concentration.

Co-release of neuropeptide Y and catecholamines upon adrenal activation in the cat.

The release of neuropeptide Y (NPY)-like immunoreactivity (-LI) in relation to catecholamines from the cat adrenal was studied in anaesthetized animals. Abdominal surgery increased plasma levels of NPY-LI from 65 +/- 6 to 149 +/- 26 pmol l-1. A positive veno-arterial concentration gradient over the adrenal gland was found for both NPY-LI, adrenaline (Adr) and noradrenaline (NA) during basal conditions.

Mechanisms underlying pre- and postjunctional effects of neuropeptide Y in sympathetic vascular control.

The effects of porcine neuropeptide Y (NPY) regarding sympathetic vascular control were studied in vitro on isolated rat blood vessels. The 10(-9)M NPY enhanced (about two-fold) the contractile responses to transmural nerve stimulation (TNS), noradrenaline (NA) and adrenaline (about two-fold) in the femoral artery. Higher concentrations of NPY (greater than 10(-8)M) caused an adrenoceptor-resistant contraction per se.

Neuropeptide Y-like immunoreactivity in adrenaline cells of adrenal medulla and in tumors and plasma of pheochromocytoma patients.

The occurrence of neuropeptide Y (NPY)-like immunoreactivity (LI) in the adrenal gland of several species as well as in tumor tissue and plasma from pheochromocytoma patients was investigated. NPY-LI was present in chromaffin cells of the adrenaline type in all species investigated except in the pig, as demonstrated by a colocalization of NPY-LI and the adrenaline-synthetizing enzyme phenylethanolamine N-methyltransferase (PNMT). NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells.