Comparative effects of intrahippocampal injection of dynorphin A(1-8), dynorphin A(1-13), dynorphin A(1-17), U-50,488H, and dynorphin B on blood pressure and heart rate in spontaneously hypertensive and normotensive Wistar-Kyoto rats. 1994

J Q Wang, and A J Ingenito
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4353.

We previously demonstrated centrally mediated hypotensive and bradycardic effects of dynorphin A(1-8) (DA1-8) on microinjection into various areas of the hippocampal formation (HF) of both anesthetized and conscious male normotensive and spontaneously hypertensive rats (SHR). The purpose of the present study was to determine whether other dynorphin fragments also had this activity. We microinjected DA1-8, dynorphin A(1-13), dynorphin A(1-17), dynorphin B (DB), and the nonpeptide kappa-opioid agonist U-50,488H into HF areas previously found to react to DA1-8, at doses ranging from 0.05 to 50 nmol. The subjects were male SHR and normotensive Wistar-Kyoto (WKY) rats in which arterial pressure and heart rate were monitored. Dose-related centrally mediated hypotension and bradycardia were found in both strains with all agents used, except for DB, which had no effects. Similarly injected drug vehicle was also without effect. In general, the responses were greater in SHR than in WKY rats. Preinjection of the active HF areas with 2 nmol of nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist, which itself had no blood pressure or heart rate effects, abolished both the decrease in blood pressure and heart rate of all dynorphins and U-50,488H. The results demonstrated the equivalent abilities of all the dynorphin fragments studied, except DB, to cause HF-mediated hypotension and bradycardia. The results with U-50,488H and nor-BNI strongly implicate kappa-opiate receptor activation of the HF in these effects.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D008297 Male Males
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D011921 Rats, Inbred WKY A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR). Rats, Wistar Kyoto,Wistar Kyoto Rat,Rats, WKY,Inbred WKY Rat,Inbred WKY Rats,Kyoto Rat, Wistar,Rat, Inbred WKY,Rat, WKY,Rat, Wistar Kyoto,WKY Rat,WKY Rat, Inbred,WKY Rats,WKY Rats, Inbred,Wistar Kyoto Rats
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic

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