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1.
Vet Rec ; 160(19): 654-7, 2007 May 12.
Article in English | MEDLINE | ID: mdl-17496272

ABSTRACT

The 5500T allele variant of the C5500T single nucleotide polymorphism in the human G protein beta3 subunit (GNB3) has been reported to be associated with primary hypertension. In this study, the GNB3 gene of primary hypertensive and normotensive dogs was examined for an analogous nucleotide polymorphism associated with hypertension. The genomic GNB3 dna, with 10 exons and nine introns coding for 340 amino acids, is described. PCR product sequencing of the GNB3 exon 9 from 25 dogs (including five hypertensive animals) failed to detect any nucleotide polymorphism. In contrast to human beings, there was no polymorphism at either the analogous nucleotide or in the respective exon. Only the human hypertension-associated thymine was detected, regardless of whether the dogs were hypertensive or normotensive. Furthermore, examinations of 565 dogs of 85 distinct breeds for the presence of the human 5500C nucleotide at the analogous nucleotide side failed to detect a cytosine that is present with high allele frequency in normotensive man. Owing to the lack of allele variance, it is concluded that canine primary hypertension is not associated with a polymorphism at either the respective human hypertension-associated nucleotide site or in the entire exon.


Subject(s)
Dog Diseases/genetics , Hypertension/veterinary , Polymorphism, Single Nucleotide , Animals , Case-Control Studies , Dogs , Exons , Female , GTP-Binding Proteins/genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , Hypertension/genetics , Male
2.
Vet Res Commun ; 21(5): 317-23, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9232775

ABSTRACT

A single intraperitoneal dose (25 mg/kg) of gossypol given to male Sprague-Dawley rats caused marked changes in the activity of the hepatic and serum gamma-glutamyltransferase (GGT) and microsomal monooxygenases. The GGT activity in liver homogenate, S-9 supernatant fraction and microsomes was significantly depressed; however, the level of serum GGT was elevated. While the hepatic glutathione concentration was not greatly changed, the aminopyrine N-demethylase activity and microsomal cytochrome P450 content of the liver were significantly decreased in the treated rats. At necropsy, the livers of the treated rats appeared generally pale with distinct pinpoint foci. Histopathological examination of the liver showed degenerative changes and coagulative necrosis. The results indicate that gossypol is a strong hepatotoxic agent which can produce severe hepatic damage.


Subject(s)
Gossypol/pharmacology , Liver/enzymology , Microsomes, Liver/enzymology , gamma-Glutamyltransferase/drug effects , Aminopyrine N-Demethylase/drug effects , Aminopyrine N-Demethylase/metabolism , Animal Feed , Animals , Cytochrome P-450 Enzyme System/drug effects , Cytochrome P-450 Enzyme System/metabolism , Glutathione/drug effects , Glutathione/metabolism , Gossypol/adverse effects , Infusions, Parenteral , Male , Microsomes, Liver/drug effects , Necrosis , Rats , Rats, Sprague-Dawley , gamma-Glutamyltransferase/metabolism
3.
Hypertension ; 9(1): 49-58, 1987 Jan.
Article in English | MEDLINE | ID: mdl-3793200

ABSTRACT

A 5-year-old female Siberian husky that was diagnosed as an essential hypertensive was bred several times over a 5-year period, producing a colony of 39 offspring. Thirty of the 39 animals were subjected to biweekly systemic arterial blood pressure determinations with femoral arterial puncture and were placed into two hypertensive and two normotensive groups based on mean blood pressure: Group 1 (mean blood pressure, 128 +/- 12 mm Hg), Group 2 (mean blood pressure, 121 +/- 3 mm Hg), Group 3 (mean blood pressure, 114 +/- 8 mm Hg), and Group 4 (mean blood pressure, 101 +/- 9 mm Hg). Groups 1, 2, and 3 had mean blood pressures significantly higher than that of Group 4 (p less than 0.05). Ten dogs (representatives from Groups 1, 2, and 3) were subjected to more detailed clinical testing including angiography, echocardiography, ophthalmic examination, plasma catecholamine and renin activity measurements, plasma lead and cadmium determinations, cerebrospinal fluid examination, renal profile, and serum chemistry and hematological analysis. Five unrelated normotensive Siberian huskies were compared with colony dogs by using echocardiography. Groups 1 and 2 showed a clear but statistically insignificant upward trend in left ventricular wall thickness indexed against body weights when compared with that in Group 3 and in the unrelated five normal Siberian dogs. Thus, the only specific difference from group to group in the colony at the termination of this study was the difference in mean blood pressure. Based on these data, it is possible and likely that aging will reveal changes secondary to chronic primary hypertension. The pathogenesis of this hereditary disorder remains unknown.


Subject(s)
Dog Diseases/genetics , Hypertension/veterinary , Animals , Disease Models, Animal , Dogs , Female , Hypertension/genetics , Male
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