Reciprocal rat chromosome 2 congenic strains reveal contrasting blood pressure and heart rate QTL

2002 ◽  
Vol 10 (3) ◽  
pp. 199-210 ◽  
Author(s):  
Adamu Alemayehu ◽  
Laura Breen ◽  
Drahomira Krenova ◽  
Morton P. Printz
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Spontaneously Hypertensive Rat ◽  
Cardiovascular Responses ◽  
Chromosome 2 ◽  
Spontaneously Hypertensive ◽  
Congenic Strains ◽  
Multiple Blood ◽  
Wistar Kyoto ◽  
Chromosome Segments

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.

Vasopressin withdrawal produces hypotension in the spontaneously hypertensive rat

1985 ◽  
Vol 249 (1) ◽  
pp. H193-H197 ◽  
Author(s):  
E. K. Chiu ◽  
J. R. McNeill
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Arginine Vasopressin ◽  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Pressor Agent

In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous infusions of either arginine vasopressin (AVP, 8 mU X kg-1 X min-1) or phenylephrine (PE, 20 nmol X kg-1 X min-1) resulted in similar rises in arterial pressure. Heart rate fell greatly in the WKY but not in the SHR. Withdrawal of the PE infusion resulted in moderate decreases in blood pressure and increases in heart rate; these responses were similar in SHR and WKY. At 5 h after PE withdrawal, blood pressure and heart rate returned to basal values. In contrast, withdrawal of the AVP infusion was associated with greater falls in blood pressure and rises in heart rate. Blood pressure and heart rate in both the SHR and the WKY at 5 h after AVP were significantly different from their respective basal values. The effects of AVP withdrawal on either blood pressure or heart rate were significantly greater in the SHR than in the WKY. At 5 h after the withdrawal of AVP, blood pressure in the SHR was reduced to normotensive levels. These results suggest that the withdrawal effect was specific to AVP, was more marked in the SHR, and might not result from only the rise in blood pressure seen during the intravenous infusion of the pressor agent.

scholarly journals Circumventricular Organ Apelin Receptor Knockdown Decreases Blood Pressure and Sympathetic Drive Responses in the Spontaneously Hypertensive Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Philip R. Griffiths ◽  
Stephen J. Lolait ◽  
Julian F. R. Paton ◽  
Anne-Marie O’Carroll
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
Circumventricular Organs ◽  
Major Question ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Apelin Receptor ◽  
Wistar Kyoto

The central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene (aplnr) expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr1]apelin-13 to the CVOs of SHRs compared to WKY rats. Lentiviral APJ-specific-shRNA (LV-APJ-shRNA) was used to knockdown aplnr expression, both collectively in three CVOs and discretely in individual CVOs, of rats implanted with radiotelemeters to measure arterial pressure. LV-APJ-shRNA-injection decreased aplnr expression in the CVOs and abolished MABP responses to microinjection of [Pyr1]apelin-13. Chronic knockdown of aplnr in any of the CVOs, collectively or individually, did not affect basal MABP in SHR or WKY rats. Moreover, knockdown of aplnr in any of the CVOs individually did not affect the depressor response to systemic [Pyr1]apelin-13. By contrast, multiple knockdown of aplnr in the three CVOs reduced acute cardiovascular responses to peripheral [Pyr1]apelin-13 administration in SHR but not WKY rats. These results suggest that endogenous APJ activity in the CVOs has no effect on basal BP but that functional APJ in the CVOs is required for an intact cardiovascular response to peripherally administered apelin in the SHR.

SHR Y chromosome enhances the nocturnal blood pressure in socially interacting rats

2000 ◽  
Vol 279 (1) ◽  
pp. H58-H66 ◽  
Author(s):  
Ann Caplea ◽  
Darcie Seachrist ◽  
Gail Dunphy ◽  
Daniel Ely
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Y Chromosome ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Nocturnal Blood Pressure ◽  
Baseline Values ◽  
Wistar Kyoto

Our objective was to test the hypothesis that nocturnal mean arterial pressure (MAP), heart rate (HR), and activity would be increased in 1) colony over individually caged rats and 2) the spontaneously hypertensive rat (SHR) Y chromosome strain (SHR/y colony) compared with Wistar-Kyoto (WKY) rats. MAP, HR, and activity were monitored using radiotelemetry. The nocturnal MAP rise expressed as the percentage change in MAP from light to dark was increased ( P < 0.05) in the SHR/y colony. The SHR Y chromosome increased MAP in both the colony and caged groups compared with WKY ( P < 0.001). The SHR/y colony animals spent 23% of a 24-h period at a MAP >120 mmHg, whereas the WKY colony animals spent 2% of a 24-h period in this range. The MAP of the SHR/y colony on clonidine was reduced ( P < 0.001) to WKY baseline values. Activity but not HR was increased ( P < 0.01) in the WKY and SHR/y colonies compared with caged animals. In conclusion, colony housing and the SHR Y chromosome increased MAP compared with individually caged housing.

scholarly journals Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats

2011 ◽  
Vol 300 (6) ◽  
pp. H1990-H1996 ◽  
Author(s):  
Houli Jiang ◽  
John Quilley ◽  
Anabel B. Doumad ◽  
Angela G. Zhu ◽  
John R. Falck ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Blood Pressure Reduction ◽  
Maximal Velocity ◽  
Spontaneously Hypertensive ◽  
Cis And Trans Isomers ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto ◽  
Cis And Trans ◽  
Cis Isomer

Epoxyeicosatrienoic acids (EETs) are vasodilator, natriuretic, and antiinflammatory lipid mediators. Both cis- and trans-EETs are stored in phospholipids and in red blood cells (RBCs) in the circulation; the maximal velocity ( Vmax) of trans-EET hydrolysis by soluble epoxide hydrolase (sEH) is threefold that of cis-EETs. Because RBCs of the spontaneously hypertensive rat (SHR) exhibit increased sEH activity, a deficiency of trans-EETs in the SHR was hypothesized to increase blood pressure (BP). This prediction was fulfilled, since sEH inhibition with cis-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid (AUCB; 2 mg·kg−1·day−1 for 7 days) in the SHR reduced mean BP from 176 ± 8 to 153 ± 5 mmHg ( P < 0.05), whereas BP in the control Wistar-Kyoto rat (WKY) was unaffected. Plasma levels of EETs in the SHR were lower than in the age-matched control WKY (16.4 ± 1.6 vs. 26.1 ± 1.8 ng/ml; P < 0.05). The decrease in BP in the SHR treated with AUCB was associated with an increase in plasma EETs, which was mostly accounted for by increasing trans-EET from 4.1 ± 0.2 to 7.9 ± 1.5 ng/ml ( P < 0.05). Consistent with the effect of increased plasma trans-EETs and reduced BP in the SHR, the 14,15- trans-EET was more potent (ED50 10−10 M; maximum dilation 59 ± 15 μm) than the cis-isomer (ED50 10−9 M; maximum dilation 30 ± 11 μm) in relaxing rat preconstricted arcuate arteries. The 11,12-EET cis- and trans-isomers were equipotent dilators as were the 8,9-EET isomers. In summary, inhibition of sEH resulted in a twofold increase in plasma trans-EETs and reduced mean BP in the SHR. The greater vasodilator potency of trans- vs. cis-EETs may contribute to the antihypertensive effects of sEH inhibitors.

Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin

1980 ◽  
Vol 59 (s6) ◽  
pp. 235s-237s ◽  
Author(s):  
R. W. Rockhold ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Hypertensive Rats ◽  
Methionine Enkephalin ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

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.

Hypoxic moderation of systemic hypertension in the spontaneously hypertensive rat

1987 ◽  
Vol 252 (3) ◽  
pp. R554-R561 ◽  
Author(s):  
W. N. Henley ◽  
A. Tucker
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Metabolic Adaptation ◽  
Systemic Hypertension ◽  
Thyroid Status ◽  
Blood Pressure Elevation ◽  
Spontaneously Hypertensive ◽  
Moderate Hypobaric Hypoxia ◽  
Hypertensive Rat ◽  
Wistar Kyoto

The mechanism by which chronic, moderate, hypobaric hypoxia attenuates systemic systolic blood pressure (SBP) in the spontaneously hypertensive rat (SHR) was investigated in a three-part study. In experiment 1, 10 wk of hypoxia (3,658 m altitude) commencing in 7-wk-old rats was partially effective in preventing the rise in SBP [hypoxic SHR (SHR-H) 154 mmHg vs. normoxic SHR (SHR-N) 180 mmHg; P less than 0.01]. When hypoxia was initiated in 5-wk-old SHR (experiments 2 and 3), protection against hypertension was nearly complete (experiment 2: SHR-H 122 mmHg vs. SHR-N 175 mmHg; P less than 0.001; experiment 3: 135 vs. 152 mmHg, respectively; P less than 0.05). Elevations in O2 consumption (VO2) and rectal temperature (Tre) in SHR vs. normotensive [Wistar-Kyoto (WKY)] rats provided evidence that the SHR is a hypermetabolic animal. Thyroid hormonal indices suggested that SHR changed from a low to high thyroid status at a time that rapid blood pressure elevation occurred; however, hypoxia did not influence thyroid status. Acute, significant decrements in VO2 and Tre in SHR-H (experiments 2 and 3) accompanied the attenuation of SBP by hypoxia, whereas large decrements in VO2 and SBP did not occur in hypoxic WKY. Timely administration of moderate hypoxia protects against the development of hypertension in the SHR. This protection may relate to a metabolic adaptation made by the hypoxic SHR.

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 ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Atrial Natriuretic Peptide ◽  
Right Ventricular ◽  
Natriuretic Peptide ◽  
Intermittent Hypoxia ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

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.

Blood pressure responsiveness during the development of hypertension in the conscious spontaneously hypertensive rat

1985 ◽  
Vol 63 (10) ◽  
pp. 1258-1262 ◽  
Author(s):  
Corey B. Toal ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Blood Pressure Response ◽  
Receptor Occupancy ◽  
Pressure Response ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Freely Moving ◽  
Wistar Kyoto

Blood pressure responsiveness to iv noradrenaline and angiotensin II was studied in conscious, freely moving, age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 to 16 weeks of age. At 4 and 6 weeks the SHR showed small, but nonsignificant increases in responsiveness compared with WKY to both noradrenaline and angiotensin II. At 8 weeks they exhibited similar responses to the WKY. Subsequently, at 12 and 16 weeks decreased responsiveness to noradrenaline (nonsignificant) and angiotensin II (p < 0.05 at 12 and 16 weeks) was observed in SHR versus WKY. At 16 weeks of age, hexamethonium caused potentiation of the blood pressure response to noradrenaline and angiotensin II, but to the same degree in the two strains. Captopril at this age did not elicit potentiation to noradrenaline or angiotensin II in either strain. These results indicate that there is no rise in blood pressure responsiveness to circulating pressor agents, parallel to the development of hypertension in SHR. Increased receptor occupancy or more active attenuating reflexes in SHR versus WKY appear not to be involved in the absence of hyperresponsiveness in intact consious SHR at 16 weeks of age.

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