Hypoxic pressor response, cardiac size, and natriuretic peptides are modified by long-term intermittent hypoxia

1999 ◽  
Vol 87 (6) ◽  
pp. 2025-2031 ◽  
Author(s):  
Holger Kraiczi ◽  
Jarkko Magga ◽  
Xiang Ying Sun ◽  
Heikki Ruskoaho ◽  
Xiaohe Zhao ◽  
...  

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.

1998 ◽  
Vol 274 (3) ◽  
pp. H794-H800 ◽  
Author(s):  
Jeffrey G. Dickhout ◽  
Robert M. K. W. Lee

The course of hypertension development in young spontaneously hypertensive rats (SHR) was studied by the measurement of changes in systolic blood pressure (BP), body weight, and heart rate (HR) at 2, 3, 4, and 6 wk of age. To achieve this, we compared inbreeding lines of SHR and Wistar-Kyoto rats (WKY) to determine if differences in BP, body weight, or HR were present among inbreeding lines of the same strain or between strains. The effect of these differences on the eventual level of BP was then assessed. We found that BP began to diverge between SHR and WKY at 4 wk of age. Significant differences in systolic BP (24 mmHg) between SHR inbreeding lines at 4 wk of age did not affect the BP at 8 wk (172 vs. 170 mmHg). Pulse pressure was significantly higher in SHR than in WKY at 4 wk of age. HR was elevated in SHR over age-matched WKY at 3 wk of age and positively correlated to the level of BP attained by individual animals at 6 wk ( P = 0.037). Moreover, WKY inbreeding lines showing elevated HR developed higher BP (145 vs. 127 mmHg) at 10–12 and 20 wk of age. The prehypertensive tachycardia in SHR was investigated further and found to result from an increased intrinsic HR. Because HR at 3 wk is a genetic trait that can be partitioned into inbreeding lines, and inbreeding lines most expressive of this trait showed the highest eventual BP, we conclude that prehypertensive tachycardia may be an important first step during hypertension development in SHR. Moreover, early elevations in HR are highly predictive ( r = 0.41) of hypertension occurrence in the animal population studied.


1980 ◽  
Vol 59 (s6) ◽  
pp. 235s-237s ◽  
Author(s):  
R. W. Rockhold ◽  
J. T. Crofton ◽  
L. Share

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.


2002 ◽  
Vol 10 (3) ◽  
pp. 199-210 ◽  
Author(s):  
Adamu Alemayehu ◽  
Laura Breen ◽  
Drahomira Krenova ◽  
Morton P. Printz

Evidence exists implying multiple blood pressure quantitative trait loci (QTL) on rat chromosome 2. To examine this possibility, four congenic strains and nine substrains were developed with varying size chromosome segments introgressed from the spontaneously hypertensive rat (SHR/lj) and normotensive Wistar-Kyoto rat (WKY/lj) onto the reciprocal genetic background. Cardiovascular phenotyping was conducted with telemetry over extended periods during standard salt (0.7%) and high-salt (8%) diets. Our results are consistent with at least three independent pressor QTL: transfer of SHR/lj alleles to WKY/lj reveals pressor QTL within D2Rat21-D2Rat27 and D2Mgh10-D2Rat62, whereas transfer of WKY/lj D2Rat161-D2Mit8 to SHR/lj reveals a depressor locus. Our results also suggest a depressor QTL in SHR/lj located within D2Rat161-D2Mgh10. Introgressed WKY/lj segments also reveal a heart rate QTL within D2Rat40-D2Rat50 which abolished salt-induced bradycardia, dependent upon adjoining SHR/lj alleles. This study confirms the presence of multiple blood pressure QTL on chromosome 2. Taken together with our other studies, we conclude that rat chromosome 2 is rich in alleles for cardiovascular and behavioral traits and for coordinated coupling between behavior and cardiovascular responses.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dao Wen Wang ◽  
Bin Xiao ◽  
Yong Wang ◽  
Xiaojun Xiong ◽  
Darryl C Zeldin

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have potent vasodilatory and diuretic feature, and therefore potentially hypotensive effect. No in vivo studies, however, were performed to support it. This study investigated the hypothesis via overexpressing CYP epoxygense genes in spontaneously hypertensive rats (SHR). Recombinant adeno-associated virus vector (rAAV) was utilized to mediate long-term transfection of CYP2J2 and CYP2C11 genes, respectively, in adult SHR, and animal systolic blood pressure (SBP) was monitored using arterial caudilis indirect manometric method. Results showed that at 2 months the urinary excretion of stable hydrolysis metabolic product of 14, 15-EE, 14–15-DHET increased by 11 and 8.7 folds in rAAV-2J2 and rAAV-2C11 groups, respectively, compared with AAV-GFP-treated rats. (2) SBP in 2J2- and 2C11-treated rats decreased from 175.0 ± 2.8mHg to 163.5 ± 5.8mmHg and 161.2 ± 6.1 mmHg, respectively, ( p <0.01) at month 2, and it is 165.0 ± 4.7 mmHg and 173.0 ± 12.8 mmHg at month 6 after gene injection (~30mmHg and ~23mmHg lowerer than that in control animals, respectively, p <0.001). (3) Before the rats were sacrificed, cardiac function tests with Pressure-Volume System showed that maximum intracardiac pressure was 202.1 ± 30.0 & 209.1 ± 17.1mmHg in two gene-treated rats, respectively, significantly lower than control (241.2 ± 18.2mmHg, p <0.01) and cardiac output in treatment rats were significantly higher than control (p<0.05). (4) Interestingly, atrial natriuretic peptide (ANP) mRNA were up-regulated 6–14 folds respectively in myocardium of 2J2 and 2C11 groups; furthermore, C-type receptor mRNA of ANP was increased in heart, lung, kidney and aorta. (5) in cultured atrial cells (HLB2G5), exogenous EETs stimulated ANP production. In conclusions, for first time our data indicates overexpression of CYP2J2 or CYP2C11 could prevent development of hypertension in SHR, improve cardiac functions, which may involve up-regulating ANP expression and its receptors in target tissues, which suppresses collagen deposition and cardiovascular remodeling.


1995 ◽  
Vol 78 (5) ◽  
pp. 1793-1799 ◽  
Author(s):  
M. Kamitomo ◽  
T. Ohtsuka ◽  
R. D. Gilbert

We exposed fetuses to high-altitude (3,820 m) hypoxemia from 30 to 130 days gestation, when we measured fetal heart rate, right and left ventricular outputs with electromagnetic flow probes, and arterial blood pressure during an isoproterenol dose-response infusion. We also measured the distribution of cardiac output with radiolabeled microspheres during the maximal isoproterenol dose. Baseline fetal arterial blood pressure was higher in long-term hypoxemic fetuses (50.1 +/- 1.3 vs. 43.4 +/- 1.0 mmHg) but fell during the isoproterenol infusion to 41.3 +/- 1.4 and 37.5 +/- 1.4 mmHg, respectively, at the highest dose. Heart rate was the same in both groups and did not differ during isoproterenol infusion. Baseline fetal cardiac output was lower in the hypoxemic group (339 +/- 18 vs. 436 +/- 19 ml.min-1.kg-1) due mainly to a reduction in right ventricular output. During the isoproterenol infusion, right ventricular output increased to the same extent in both hypoxemic and normoxic fetuses (approximately 35%); however, left ventricular output increased only approximately 15% in the hypoxemic group compared with approximately 40% in the normoxic group. The percent change in individual organ blood flows during isoproterenol infusion in the hypoxemic groups was not significantly different from the normoxic group. All of the mechanisms that might be responsible for the differential response of the fetal left and right ventricles to long-term hypoxia are not understood and need further exploration.


1990 ◽  
Vol 258 (1) ◽  
pp. C109-C114 ◽  
Author(s):  
M. K. Raizada ◽  
B. Kimura ◽  
M. I. Phillips

Neuronal and glial cultures from the hypothalamic-brain stem areas of 1-day-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rat brains stained positively with atrial natriuretic peptide (ANP)-specific antibodies. The endogenous levels of the ANP immunoreactivity in WKY neuronal and glial cultures were 17.0 +/- 2.2 and 14.3 +/- 2.7 pg/mg, respectively. Comparable neuronal and glial cultures from SH rat brains contained a 48 to 70% decrease in the endogenous ANP immunoreactivity levels. Culture media from both brain cell types also contained ANP immunoreactivity, the levels of which are significantly higher than those found in the cells. However, similar to endogenous levels, the media levels of immunoreactive ANP in SH neuronal and glial cultures were significantly reduced compared with WKY brain cultures. These observations demonstrate that endogenous ANP-like immunoreactivity is found in neuronal and glial cells and is released into the media. The levels of peptide are reduced in cultures of SH compared with WKY cultures, suggesting a genetically controlled difference between the hypertensive and normotensive rat strains long before hypertension develops.


2011 ◽  
Vol 12 (4) ◽  
pp. 394-403 ◽  
Author(s):  
Silmara Ciampone ◽  
Rafael Borges ◽  
Ize P de Lima ◽  
Flávia F Mesquita ◽  
Elizabeth C Cambiucci ◽  
...  

Observations have been made regarding the effects of long-term exercise training on blood pressure, renal sodium handling and renal renin–angiotensin–aldosterone (RAS) intracellular pathways in conscious, trained Okamoto–Aoki spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKy) normotensive rats, compared with appropriate age-matched sedentary SHR and WKy. To evaluate the influence of exercise training on renal function and RAS, receptors and intracellular angiotensin II (AngII) pathway compounds were used respectively, and lithium clearance and western blot methods were utilised. The current study demonstrated that increased blood pressure in SHR was blunted and significantly reduced by long-term swim training between the ages of 6 and 16 weeks. Additionally, the investigators observed an increased fractional urinary sodium excretion in trained SHR (SHRT) rats, compared with sedentary SHR (SHRS), despite a significantly decreased creatinine clearance (CCr). Furthermore, immunoblotting analysis demonstrated a decreased expression of AT1R in the entire kidney of TSHR rats, compared with SSHR. Conversely, the expression of the AT2R, in both sedentary and trained SHR, was unchanged. The present study may indicate that, in the kidney, long-term exercise exerts a modulating effect on AngII receptor expression. In fact, the present study indicates an association of increasing natriuresis, reciprocal changes in renal AngII receptors and intracellular pathway proteins with the fall in blood pressure levels observed in TSHR rats compared with age-matched SSHR rats.


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