Cardiovascular effects and modulation of noradrenergic neurotransmission following central and peripheral administration of neuropeptide Y.
Experiments have been conducted to evaluate the effect of neuropeptide Y (NPY) administered at three distinct levels of the nervous system: 1) the posterior hypothalamic nucleus, 2) the spinal cord, and 3) the vascular noradrenergic neuroeffector junction. It was observed that NPY produced varying cardiovascular effects at these three distinct sites of the nervous system. Microinjections into the posterior hypothalamic nucleus resulted in an increase in blood pressure, which was reduced by prior microinjection of a muscarinic or H1-histamine antagonist but not an H2-histamine antagonist. In addition to the involvement of histaminergic and cholinergic pathways, the pressor effect of NPY appears to result from an increase in sympathetic outflow. NPY was also seen to decrease the potassium-induced release of norepinephrine (NE) from slices obtained from the posterior hypothalamic nucleus. In contrast to what was observed in the hypothalamus, the intrathecal injection of NPY at a level of T4 or T10 in anesthetized or T10 in unanesthetized rats resulted in a depressor effect as well as a decrease in heart rate. Both an alpha 2- and beta-adrenoceptor antagonist reduced the NPY effect. The depressor effect of intrathecal NPY was attenuated in rats pretreated with reserpine as well as in Spontaneously Hypertensive rats (SHR). These data suggest that the effects of NPY are closely associated with sympathetic preganglionic neurons in the spinal cord. At the vascular noradrenergic neuroeffector junction, NPY decreased the nerve stimulation-induced release of NE while potentiating the contractile response. Moreover, NPY potentiated the increase in perfusion pressure of the perfused mesenteric arterial bed in response to angiotensin, vasopressin, or phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
Westfall
T C
TC
Department of Pharmacology, St. Louis University School of Medicine, Missouri 63104.
Martin
J
J
Chen
X L
XL
Ciarleglio
A
A
Carpentier
S
S
Henderson
K
K
Knuepfer
M
M
Beinfeld
M
M
Naes
L
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000502:physiology*; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D008845:Microinjections; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012016:Reference Values; D013045:Species Specificity; D009435:Synaptic Transmission / Q000187:drug effects*
D009478:Neuropeptide Y; D006632:Histamine; D002217:Carbachol; D009638:Norepinephrine