Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness

2002 ◽  
Vol 11 (2) ◽  
pp. 65-72 ◽  
Author(s):  
Imran M. Khan ◽  
Erin Singletary ◽  
Adamu Alemayehu ◽  
Shanaka Stanislaus ◽  
Morton P. Printz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gene Cluster ◽  
Nicotinic Receptor ◽  
Receptor Gene ◽  
Repeated Administration ◽  
Chromosome 8 ◽  
Brown Norway ◽  
Spontaneously Hypertensive ◽  
Nicotinic Agonists ◽  
Nociceptive Responses

Spontaneously hypertensive rats (SHR) exhibit enhanced pressor, heart rate, and nociceptive responses to spinal nicotinic agonists. This accompanies a paradoxical decrease in spinal nicotinic receptor number in SHR compared with normotensive rats. The congenic strain, SHR-Lx, with an introgressed chromosome 8 segment from the normotensive Brown-Norway-Lx strain (BN-Lx) exhibits reduced blood pressure. This segment contains a gene cluster for three nicotinic receptor subunits expressed in the nervous system. We examined the implication of this gene cluster in the enhanced responsiveness of the SHR. Pressor and nociceptive responses to spinal cytisine, a nicotinic agonist, were diminished in SHR-Lx. Moreover, with repeated administration, these responses desensitized faster in SHR-Lx and progenitor BN-Lx than in progenitor SHR/Ola. This implicates the gene cluster in both cardiovascular and nociceptive responses to spinal nicotinic agonists. Since diminished responsiveness to agonist stimulation is greater than the basal blood pressure differences between the strains and the introgressed rat chromosome maps to a quantitative trait locus in human hypertension, polymorphisms in the three nicotinic receptor genes become candidates for altered central control of blood pressure.

scholarly journals Effects of Transgenic Expression of Dopamine Beta Hydroxylase (Dbh) Gene on Blood Pressure in Spontaneously Hypertensive Rats

2016 ◽  
pp. 1039-1044
Author(s):  
M. PRAVENEC ◽  
V. LANDA ◽  
V. ZÍDEK ◽  
P. MLEJNEK ◽  
J. ŠILHAVÝ ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Spontaneously Hypertensive Rat ◽  
Reduce Blood Pressure ◽  
Left Ventricular ◽  
Brown Norway ◽  
Catecholamine Metabolism ◽  
Mrna Levels ◽  
Spontaneously Hypertensive ◽  
Dopamine Beta Hydroxylase

The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and left ventricular hypertrophy. Catecholamines play an important role in the pathogenesis of both essential hypertension in humans and in the SHR. Recently, we obtained evidence that the SHR harbors a variant in the gene for dopamine beta hydroxylase (Dbh) that is associated with reduced adrenal expression of Dbh mRNA and reduced DBH enzymatic activity which correlated negatively with blood pressure. In the current study, we used a transgenic experiment to test the hypothesis that reduced Dbh expression predisposes the SHR to hypertension and that augmentation of Dbh expression would reduce blood pressure. We derived 2 new transgenic SHR-Dbh lines expressing Dbh cDNA under control of the Brown Norway (BN) wild type promoter. We found modestly increased adrenal expression of Dbh in transgenic rats versus SHR non-transgenic controls that was associated with reduced adrenal levels of dopamine and increased plasma levels of norepinephrine and epinephrine. The observed changes in catecholamine metabolism were associated with increased blood pressure and left ventricular mass in both transgenic lines. We did not observe any consistent changes in brainstem levels of catecholamines or of mRNA levels of Dbh in the transgenic strains. Contrary to our initial expections, these findings are consistent with the possibility that genetically determined decreases in adrenal expression and activity of DBH do not represent primary determinants of increased blood pressure in the SHR model.

Ablation of primary afferent terminals reduces nicotinic receptor expression and the nociceptive responses to nicotinic agonists in the spinal cord

2004 ◽  
Vol 33 (5) ◽  
pp. 543-556 ◽  
Author(s):  
Imran M. Khan ◽  
Michelle Wennerholm ◽  
Erin Singletary ◽  
Kimberley Polston ◽  
Limin Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nicotinic Receptor ◽  
Receptor Expression ◽  
Primary Afferent ◽  
Nicotinic Agonists ◽  
Nociceptive Responses ◽  
Afferent Terminals

Interaction between nitric oxide and renal myogenic autoregulation in normotensive and hypertensive rats

2001 ◽  
Vol 79 (3) ◽  
pp. 238-245 ◽  
Author(s):  
Xuemei Wang ◽  
William A Cupples
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Wistar Rats ◽  
Fundamental Property ◽  
Brown Norway ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Long Evans

Blood pressure fluctuates continuously throughout life and autoregulation is the primary mechanism that isolates the kidney from this fluctuation. Compared with Wistar rats, Brown Norway (B-N) rats display impaired renal myogenic autoregulation when blood pressure fluctuation is increased. They also are very susceptible to hypertension-induced renal injury. Because blockade of nitric oxide augments myogenic autoregulation in Wistar rats, we compared the response of the myogenic system in B-N rats to nitric oxide blockade with that of other strains [Wistar, Sprague-Dawley, Long-Evans, spontaneously hypertensive (SHR)]. Renal blood flow dynamics were assessed in isoflurane anesthetized rats before and after inhibition of nitric oxide synthase by Lω-nitro-arginine methyl-ester (L-NAME, 10 mg/kg, iv). Under control conditions, myogenic autoregulation in the B-N rats was weaker than in the other strains. Myogenic autoregulation was not augmented after L-NAME administration in the SHR, but was augmented in all the normotensive rats. The enhancement was significantly greater in B-N rats so that after L-NAME the efficiency of autoregulation did not differ among the strains. The data suggest that nitric oxide is involved in the impaired myogenic autoregulation seen in B-N rats. Furthermore, the similarity of response in Wistar, Long-Evans, and Sprague-Dawley rats suggests that modulation by nitric oxide is a fundamental property of renal myogenic autoregulation.Key words: renal blood flow, transfer function, dynamics, SHR, Wistar, Long-Evans, Sprague-Dawley, Brown-Norway, L-NAME.

Renal renin activity is associated with alterations of the renin gene in recombinant inbred rat strains

1993 ◽  
Vol 84 (2) ◽  
pp. 129-132 ◽  
Author(s):  
Irena Pohlová ◽  
Josef Zicha ◽  
Vladimir Křen ◽  
Jaroslav Kuneš ◽  
Michal Pravenec
Keyword(s):  
Blood Pressure ◽  
Recombinant Inbred ◽  
Spontaneously Hypertensive Rat ◽  
Inbred Strains ◽  
Renin Activity ◽  
Recombinant Inbred Strains ◽  
Brown Norway ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Renin Gene

1. A structural alteration within the first intron of the renin gene in spontaneously hypertensive rats was demonstrated to co-segregate with blood pressure in some sets of F2 hybrids or recombinant inbred strains. There is no evidence as to whether restriction fragment length polymorphism of the renin gene is associated with any of the changes in the renin tissue level. For this reason we have determined renal renin activity in spontaneously hypertensive, Wistar-Kyoto and Brown Norway rats as well as in 22 recombinant inbred strains derived from F2 hybrids of spontaneously hypertensive and Brown Norway rats. 2. At the age of 4 months significantly lower renal renin activity was observed in spontaneously hypertensive rats than in both normotensive rat strains, Wistar-Kyoto and Brown Norway. The presence of the spontaneously hypertensive rat allele in recombinant inbred strains was associated with a substantially lower renal renin activity as compared with recombinant inbred strains bearing the Brown Norway rat allele. There was no relationship between renal renin activity and the polymorphism in either the angiotensinogen gene or the angiotensin-converting enzyme gene. 3. There was a borderline correlation between blood pressure and renal renin activity in recombinant inbred strains. Nevertheless, additional comparisons within recombinant inbred strains bearing the spontaneously hypertensive rat allele of the renin gene failed to reveal any significant relationship between blood pressure level and renal renin activity. 4. Our data suggest that the restriction fragment length polymorphism marking the renin gene of the spontaneously hypertensive rat is accompanied by an alteration in the renin-angiotensin system at the renal level. The mechanisms by which structural abnormalities of the renin gene might influence the renin level in the kidney remain to be investigated.

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