Regional brain concentrations of several putative peptide neurotransmitters in normotensive and spontaneously hypertensive rats: effects of continuous (10-day) clonidine infusion.
In the present study, the mean arterial pressures (MAP) and heart rates (HR) were measured in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) that had received a 10-day continuous subcutaneous infusion of either saline or the centrally acting alpha-adrenoceptor agonist clonidine (10 micrograms/kg/h). In separate groups of similarly treated rats, the concentrations of neurotensin (NT), vasoactive intestinal polypeptide (VIP), cholecystokinin octapeptide (CCK-8), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were measured in the cortex (COR), hypothalamus (HYP), medulla oblongata/pons (MO/P), and cervical (CSC) and thoracic (TSC) spinal cord. In comparison to the WKY rats, the SHR had significantly lower neuropeptide concentrations within the COR (NPY, CCK-8), HYP (NT), MO/P (NPY, NT, and CCK-8), CSC (all neuropeptides), and TSC (NPY, NT, CCK-8, and VIP). The infusion of clonidine lowered the MAP of the WKY and SHR rats (-10 and -35 mm Hg, as compared with respective saline controls) and HR in the WKY rats (-45 beats/min). In general, the infusion of clonidine produced decreases in neuropeptide levels within the CNS of the WKY rather than the SHR strain. When there was a strain difference (i.e., SHR less than WKY), it was evident, particularly within the spinal cord, that clonidine reduced the levels of the neuropeptides in the WKY rats to those levels in the SHR. These findings suggest that the reduced neuropeptide concentrations of the SHR (particularly those within the CSC) and TSC may be a result of, rather than a causal factor in, hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Jarrott
B
B
University of Melbourne, Department of Clinical Pharmacology, Victoria, Australia.
Lewis
S J
SJ
Louis
W J
WJ
Maccarrone
C
C
Shulkes
A
A
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000378:metabolism*; D007260:Infusion Pumps; D007263:Infusions, Parenteral; D009478:Neuropeptide Y / Q000032:analysis; D009479:Neuropeptides / Q000032:analysis*; D009496:Neurotensin / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012844:Sincalide / Q000032:analysis; D013116:Spinal Cord / Q000032:analysis / Q000187:drug effects
D009478:Neuropeptide Y; D009479:Neuropeptides; D009496:Neurotensin; D012844:Sincalide; D003000:Clonidine