Document Detail

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat.
MedLine Citation:
PMID:  20952662     Owner:  NLM     Status:  MEDLINE    
The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6-38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6-38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined.
Melissa M J Farnham; Melissa A Inglott; Paul M Pilowsky
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-15
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  300     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H214-22     Citation Subset:  IM    
Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
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MeSH Terms
Analysis of Variance
Blood Pressure / drug effects*
Fluorescent Antibody Technique
Heart Rate / drug effects*
Hypertension / metabolism,  physiopathology*
In Situ Hybridization
Injections, Spinal
Medulla Oblongata / drug effects*,  metabolism,  physiopathology
Neurons / drug effects*,  metabolism
Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism,  pharmacology*
RNA, Messenger / metabolism
Rats, Inbred SHR
Rats, Inbred WKY
Species Specificity
Sympathetic Nervous System / drug effects*,  metabolism,  physiopathology
Tachycardia / chemically induced
Tyrosine 3-Monooxygenase / metabolism
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Pituitary Adenylate Cyclase-Activating Polypeptide; 0/RNA, Messenger; 0/Vasodilator Agents; EC 3-Monooxygenase

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