Kinin B1 and B2 receptor mRNA expression in the hypothalamus of spontaneously hypertensive rats

2002 ◽  
Vol 80 (4) ◽  
pp. 258-263 ◽  
Author(s):  
F Qadri ◽  
W Häuser ◽  
O Jöhren ◽  
P Dominiak

The central hypertensive effects induced by bradykinin are known to be mediated via B2 receptors, which are present constitutively in the brain. B1 receptors are rapidly upregulated during inflammation, hyperalgesia, and experimental diabetes. The hypothalamus plays an important role in the regulation of cardiovascular homeostasis, and all components of kallikrein–kinin system have been identified in this area. Therefore, we analyzed the mRNA expression of B1 and B2 receptors in the hypothalamus of spontaneously hypertensive rats (SHR) by RT-PCR. Male SHR were studied at three different ages corresponding to the three phases in the development of hypertension: (i) 3–4 (prehypertensive), (ii) 7–8 (onset of hypertension), and (iii) 12–13 weeks (established hypertension) after birth, and compared with age-matched Wistar–Kyoto (WKY) rats. At all ages tested, B2 receptor mRNA levels in the hypothalamus of SHR were higher than age-matched WKY rats (p < 0.001). However, the B1 receptor mRNA levels were higher at the established phase of hypertension only. We conclude that B1 and B2 receptor mRNA are differentially expressed in the hypothalamus of SHR and may play different roles in the pathogenesis of hypertension: upregulation of B2 receptor mRNA from early age may participate in the pathogenesis of hypertension, whereas an upregulation of B1 receptor mRNA in the established phase of hypertension may reflect an epiphenomenon in essential hypertension.Key words: kinin receptors, mRNA expression, hypothalamus, SHR, WKY.

2010 ◽  
Vol 299 (1) ◽  
pp. R291-R297 ◽  
Author(s):  
Cristiana A. Ogihara ◽  
Gerhardus H. M. Schoorlemmer ◽  
Adriana C. Levada ◽  
Tania C. Pithon-Curi ◽  
Rui Curi ◽  
...  

Inhibition of the commissural nucleus of the solitary tract (commNTS) induces a fall in sympathetic nerve activity and blood pressure in spontaneously hypertensive rats (SHR), which suggests that this subnucleus of the NTS is a source of sympathoexcitation. Exercise training reduces sympathetic activity and arterial pressure. The purpose of the present study was to investigate whether the swimming exercise can modify the regional vascular responses evoked by inhibition of the commNTS neurons in SHR and normotensive Wistar-Kyoto (WKY) rats. Exercise consisted of swimming, 1 h/day, 5 days/wk for 6 wks, with a load of 2% of the body weight. The day after the last exercise session, the rats were anesthetized with intravenous α-chloralose, tracheostomized, and artificially ventilated. The femoral artery was cannulated for mean arterial pressure (MAP) and heart rate recordings, and Doppler flow probes were placed around the lower abdominal aorta and superior mesenteric artery. Microinjection of 50 mM GABA into the commNTS caused similar reductions in MAP in swimming and sedentary SHR (−25 ± 6 and −30 ± 5 mmHg, respectively), but hindlimb vascular conductance increased twofold in exercised vs. sedentary SHR (54 ± 8 vs. 24 ± 5%). GABA into the commNTS caused smaller reductions in MAP in swimming and sedentary WKY rats (−20 ± 4 and −16 ± 2 mmHg). Hindlimb conductance increased fourfold in exercised vs. sedentary WKY rats (75 ± 2% vs. 19 ± 3%). Therefore, our data suggest that the swimming exercise induced changes in commNTS neurons, as shown by a greater enhancement of hindlimb vasodilatation in WKY vs. SHR rats in response to GABAergic inhibition of these neurons.


1986 ◽  
Vol 250 (6) ◽  
pp. R1007-R1013
Author(s):  
K. Ota ◽  
L. Share ◽  
J. T. Crofton ◽  
D. P. Brooks

Enkephalins are found in the posterior pituitary, can alter vasopressin secretion, and have greater pressor effects in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rats. Measurement of the plasma methionine-enkephalin concentration (PMet-Enk) has provided equivocal results in humans and has not been reported in rats. We have developed a highly specific and sensitive Met-Enk radioimmunoassay and determined that Met-Enk circulates in rats but that PMet-Enk is no different between SHR and WKY rats (7.6 +/- 0.8 and 9.2 +/- 0.8 pg/ml, respectively). Water deprivation for 48 h increased the plasma vasopressin concentration (PADH) and 24-h urinary vasopressin excretion (UADHV) in SHR and WKY rats, but PMet-Enk was not altered. There were no differences in PADH and UADHV between SHR and WKY rats in either the euhydrated or dehydrated state. These results suggest that it is unlikely that circulating Met-Enk contributes importantly to the maintenance of hypertension in SHR. There was also no evidence for a greater secretion of vasopressin in SHR than in WKY rats, in contrast to previous reports.


1999 ◽  
Vol 277 (4) ◽  
pp. R1057-R1062 ◽  
Author(s):  
Takahiro Nagayama ◽  
Takayuki Matsumoto ◽  
Makoto Yoshida ◽  
Mizue Suzuki-Kusaba ◽  
Hiroaki Hisa ◽  
...  

We investigated the role of nicotinic and muscarinic receptors in secretion of catecholamines induced by transmural electrical stimulation (ES) from isolated perfused adrenal glands of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. ES (1–10 Hz) produced frequency-dependent increases in epinephrine (Epi) and norepinephrine (NE) output as measured in perfusate. The ES-induced increases in NE output, but not Epi output, were significantly greater in adrenal glands of SHRs than in those of WKY rats. Hexamethonium (10–100 μM) markedly inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs and WKY rats. Atropine (0.3–3 μM) inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs, but not from those of WKY rats. These results suggest that endogenous acetylcholine-induced secretion of adrenal catecholamines is predominantly mediated by nicotinic receptors in SHRs and WKY rats and that the contribution of muscarinic receptors may be different between these two strains.


2003 ◽  
Vol 89 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Sophie Robin ◽  
Véronique Maupoil ◽  
Frédérique Groubatch ◽  
Pascal Laurant ◽  
Alain Jacqueson ◽  
...  

The objectives of the present work were to evaluate the effect of a methionine-supplemented diet as a model of hyperhomocysteinaemia on the systolic blood pressure (BP) and vasomotor functions of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR rats, randomised into four groups, were fed a normal semisynthetic diet or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was measured non-invasively. At the end of the experiment, plasma homocysteine, methionine, cysteine and glutathione levels were determined. Vasoconstriction and vasodilatation of aortic rings were measured. The methionine-supplemented diet induced a significant increase in plasma homocysteine and methionine concentration in both WKY and SHR rats, an increase in plasma cysteine concentrations in WKY rats and an increase in the glutathione concentration in SHR. The systolic BP of WKY rats fed the methionine-supplemented diet increased significantly (P<0·01), whereas systolic BP was reduced in SHR. An enhanced aortic responsiveness to noradrenaline and a decreased relaxation induced by acetylcholine and bradykinin were observed in the WKY rats fed the methionine-enriched diet. In SHR, the bradykinin-induced relaxation was reduced, but the sodium nitroprusside response was increased. In conclusion, a methionine-enriched diet induced a moderate hyperhomocysteinaemia and an elevated systolic BP in WKY rats that was consistent with the observed endothelial dysfunction. In SHR, discrepancies between the decreased systolic BP and the vascular alterations suggest more complex interactions of the methionine-enriched diet on the systolic BP. Further investigations are needed to understand the paradoxical effect of a methionine-rich diet on systolic BP.


1986 ◽  
Vol 64 (3) ◽  
pp. 284-289 ◽  
Author(s):  
Sunil Datar ◽  
William H. Laverty ◽  
J. Robert McNeill

Pressor responses and heart rate responses to intravenous injections (3.5–50.0 pmol/kg) of arginine vasopressin (AVP) were recorded in saline- and clonidine-treated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Clonidine (20 μg/kg, i. v.) caused a marked fall of arterial pressure in SHR but not in WKY rats so that, 20 min after the injection of the α2-adrenoceptor agonist, arterial pressure was similar in the two strains of rats. The curve expressing the relationship between the dose of AVP and the increase of arterial pressure for saline-treated SHR was positioned to the left of that for saline-treated WKY rats. This enhanced pressor responsiveness of SHR to AVP may have been related to impaired reflex activity since heart rate fell much less in SHR than in WKY rats for a given elevation in pressure. Pressure responses to AVP were augmented by clonidine in both SHR and WKY rats so that, similar to saline-treated rats, pressor responsiveness to the peptide was still greater in SHR. Heart rate responses to AVP were not altered significantly by clonidine. The results indicate that clonidine fails to enhance reflex activity and reduce pressor responsiveness of SHR to AVP. The increased pressor responsiveness of both SHR and WKY rats to AVP following clonidine was an unexpected finding and may be related to a peripheral interaction between α-adrenergic agonists and AVP.


Author(s):  
Jennifer Sayler ◽  
Linda Tennison ◽  
David Mitchell

Millions of children and adults worldwide are diagnosed with Attention-deficit hyperactivity disorder (ADHD) and yet its very existence, definition, and treatment are surrounded with discord and controversy. ADHD and its treatments are brought together through this investigation into the effects that drug therapy has on Wistar Kyoto rats (WKY) and a strain of Spontaneously Hypertensive rats (SHR) selectively inbred from WKY rats. The effects of the drug d-threo-methylphenidate hydrochloride (d-MPH - the d-isomer of the ADHD drug Ritalin) on spatial working memory abilities, overall growth rate, blood glucose levels, blood pH, and erythrocyte membrane lipids were examined in the two rat strains. Although all four physiological properties remained constant and normal over the course of the experiment, the spatial working memory abilities were inhibited in WKY rats receiving the drug. These results suggest that the d-isomer of this drug may have a significant impact on cognitive function in rats and possibly humans.


2007 ◽  
Vol 292 (1) ◽  
pp. E16-E23 ◽  
Author(s):  
Barbara Peters ◽  
Philipp Teubner ◽  
Susanne Clausmeyer ◽  
Tanja Puschner ◽  
Christiane Maser-Gluth ◽  
...  

ANG II and potassium are known to increase steroidogenic acute regulatory protein (StAR) levels. However, a corresponding increase in StAR mRNA levels has so far been observed only in response to ANG II. We therefore studied the regulation of adrenal StAR mRNA expression in the context of dietary potassium-stimulated aldosterone production. Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were fed a diet containing either 1 or 4% KCl for 5 days. The high-potassium diet increased StAR mRNA levels within the zona glomerulosa in both strains, as demonstrated by in situ hybridization. However, aldosterone production increased in WKY but not in SHR (WKY: from 22.8 ± 4.8 to 137 ± 25 ng/100 ml, P < 0.001, vs. SHR: from 29 ± 3.8 to 51 ± 10.2 ng/100 ml, not significant). This increase was associated with an increase in Cyp11b2 mRNA levels in WKY (3-fold; P < 0.001) but not in SHR. In both strains, the 4% KCl diet was associated with increased plasma renin-independent aldosterone production, as indicated by the marked increase of the aldosterone-to-renin ratios (from 1.4 ± 0.3 to 9 ± 3 in WKY and from 3 ± 1 to 14 ± 5 in SHR; P < 0.002). We conclude that an increase of StAR mRNA levels within the outer cortex is involved in the long-term adrenal response to potassium. This increase alone is not sufficient to increase aldosterone production in the presence of normal Cyp11b2 mRNA levels.


Hypertension ◽  
1995 ◽  
Vol 25 (4) ◽  
pp. 524-530 ◽  
Author(s):  
Imran M. Khan ◽  
Donald H. Miller ◽  
Judy Strickland ◽  
Harry S. Margolius ◽  
Philip J. Privitera

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