Indirect Systolic Blood Pressure Research Articles

Ultrasonographic kidney length-to-abdominal aortic diameter for the diagnosis of feline chronic kidney disease: A preliminary study.

Chronic kidney disease (CKD) is one of the most important diseases in cats. This study aimed to compare the ultrasonographic kidney length-to-abdominal aortic diameter (K/AO) ratio between healthy and CKD cats and investigate the correlation between K/AO and blood results. Fifteen healthy cats and 15 CKD cats were included in this clinically prospective study. All cats were evaluated for radiographic and ultrasonographic K, radiographic K-to-second lumbar length ratio (K/L2), and K/AO, indirect systolic blood pressure and plasma creatinine (Cr), blood urea nitrogen (BUN), and symmetric dimethyl arginine (SDMA). The radiographic and ultrasonographic kidney lengths of CKD were significantly shorter than those of healthy cats (p < 0.05 and p < 0.05, respectively). The average K/L2 and K/AO were significantly lower in CKD than in healthy cats (p < 0.01 and p < 0.001, respectively). The K/AO had a strong negative correlation with plasma Cr (r = -0.7682, p < 0.0001), BUN (r = -0.6175, p < 0.001), and SDMA (r = -0.589, p < 0.001). However, K/L2 had a moderate negative correlation with plasma Cr (r = -0.5866, p < 0.001), BUN (r = -0.4884, p < 0.01), and SDMA (r = -0.5404, p < 0.01). The optimal cutoff value of K/AO (<10.71) had higher sensitivity and specificity than K/L2 for identifying feline CKD. Kidney length-to-abdominal aortic diameter could be a better and more promising parameter than the K/L2 ratio for evaluating kidney size in cats with CKD.

Aging in Cats: Owner Observations and Clinical Finding in 206 Mature Cats at Enrolment to the Cat Prospective Aging and Welfare Study.

Two hundred and six cats, aged between 7 and 10 years, from the North-west of the UK, were enrolled in a cat aging and welfare study to determine the frequency of age-related conditions and associations with husbandry, owner observations of physical appearance, activity and behavior. This is the largest study to date of mature cats that includes data from an owner questionnaire and clinical examinations. At enrolment, owners frequently reported physical changes (53%), behavioral changes (47%), changes to eating patterns (41%), and activity changes (40%) in their mature cats. On physical examination, 45% cats were in overweight condition and 12% were obese. A heart murmur was detected in 29% cats, whilst indirect systolic blood pressure (SBP) was >160 mmHg in 5% cats. Dental disease was present in 54% cats and was associated with a matted hair coat (P = 0.01), increased sleeping (P = 0.02), absence of gray hairs (P = 0.03), and increased irritability to other pets (P = 0.04). Abnormalities were evident in 58% of cats that allowed an orthopedic examination (OE) to be performed. These cats were older than cats with a normal OE (P = 0.01), and abnormal OE findings were associated with a matted coat (P = 0.03) and increased grooming (P = 0.04). Aazotaemia was present in 10% cats, and this was associated with cats being observed to “sniff their food and then walk away” (P = 0.04). Hyperthyroidism was diagnosed in 3% cats, who were older (P = 0.02), had a leaner BCS (P = 0.02) and lesser blood creatinine concentrations (P = 0.01). Hyperthyroid cats were also more likely to have increased liver enzyme activity and increased SBP (P = <0.001) compared with non-hyperthyroid cats. Of the 176 cats where all clinical assessments were conducted, only 12% had no evidence of any disease. Clinical abnormalities are commonly identified when thorough, clinical assessments are performed in mature pet cats visiting primary care practice.

Use of Amlodipine in Psittacine Birds: 5 Cases (2010-2018).

Amlodipine is a calcium channel blocker shown to be effective in lowering blood pressure with minimal adverse effects in mammals. To provide a retrospective evaluation of amlodipine use in psittacine birds, medical records were reviewed for all avian patients prescribed amlodipine for treatment for the presumptive diagnosis of hypertension, based on clinical signs and indirect blood pressure measurements. Five birds were treated with amlodipine between 2010 and 2018. The median age was 33 years (range, 22-37 years) and 3/5 birds presented for ataxia or seizures. The median indirect systolic blood pressure at diagnosis was 243 mm Hg (range, 200-275 mm Hg). In 3/5 birds, amlodipine was the only drug prescribed, whereas, in 2/5 birds, enalapril was also prescribed in addition to amlodipine. In addition to the prescription of enalapril, blood pressure measurements were obtained indirectly, which are variables to be considered in this report. The initial median dose of amlodipine prescribed was 0.4 mg/kg (range, 0.1-0.4 mg/kg) PO q24h. In 3/5 birds, amlodipine administration was increased either in dose or frequency. Median follow-up time was 25 months (range, 2-55 months) after the initiation of amlodipine treatment. Owners in all 5 cases reported improvement of clinical signs by a median time of 2 months (range, 1-15 months). Three of 5 birds (60%) demonstrated a decreasing trend in blood pressure during the first 6 months after treatment with amlodipine was started (average, ≥20% decrease). Prospective, controlled studies are needed to investigate the efficacy of amlodipine in psittacine birds.

Cross-sex testosterone therapy modifies the renal morphology and function in female rats and might underlie increased systolic pressure.

Testosterone esters are hormones commonly used for affirming gender identity in transmen. The present study evaluates the effect of testosterone on renal morphology and function in an animal model submitted to cross-sex hormone therapy used for transmen. Two-month-old Wistar rats were divided into three groups: male control (MC), female control (FC), and female on testosterone therapy (FTT). The FTT group received testosterone cypionate (3.0mg/kg, i.m.), and the MC and MF groups received vehicle oil every 10days for 4months. Renal function and indirect systolic blood pressure (SBP) measurements were evaluated at 6months of age. Plasma and urine concentrations of urea, creatinine, sodium, potassium, osmolality, and glomerular filtration rate (GFR) were measured. The kidneys were weighed, paraffin-embedded, and histological sections were prepared to evaluate the glomerular area. We verified that the FTT group, in comparison to FC, had increased kidney weight [MC,3.2±0.05; FC,1.8±0.04; FTT,2.2±0.06; g], decreased urine osmolarity [MC,486.9±18.3; FC,1012.0±5.4; FTT,768.2±40.3mOsm/L/g kw], reduced GFR [MC,0.77±0.04; FC,0.78±0.02; FTT,0.67±0.03; mL/min/gkw], larger glomerular area [MC,9334±120.8; FC,7884±112.8; FTT,9078±133.4µm2 ], and higher SBP [MC,126±3.4; FC,119±1.0; FTT,131±1.4; mmHg]. Sodium excretion was higher in FC and FTT in comparison to MC [MC,0.34±0.05; FC,0.56±0.06; FTT,0.54±0.04; mEq/24h/g kw]. Cross-sex hormone therapy with testosterone in female rats induces renal morphofunctional changes and may underlie increased systolic pressure, suggesting an adaptation similar to what is observed in transmen on long-term testosterone therapy.

Evaluation of orally administered telmisartan for the reduction of indirect systolic arterial blood pressure in awake, clinically normal cats.

The aim of this study was to compare the effects of multiple once- or twice-daily oral dosage rates of the angiotensin II, type-1 receptor blocker, telmisartan (TEL), or placebo (PLA) on indirect systolic arterial blood pressure (SBP) in awake, clinically normal cats. Utilizing an incomplete crossover design and following a 14 day acclimation period, 28 healthy laboratory cats were randomized to undergo treatment with three of the following 14 day treatment protocols, each separated by a 1 week washout period: oral PLA q24h, oral TEL at a dosage of 1, 1.5, 2 or 3 mg/kg q24h, or oral TEL at a dosage of 1 or 1.5 mg/kg q12h. Using the Doppler ultrasound method, indirect SBP was measured daily during each treatment period, and daily during the first 5 days of each washout period, approximately 3 h after administration of the morning treatment. Each treatment protocol was administered to a total of 12 cats. A statistically significant effect of treatment period was identified for the entire study; therefore, only data from the first treatment period (four cats per treatment group) were used for further analysis. Compared with PLA, during the first treatment period, SBP values were significantly lower in cats treated with TEL at all tested dosages by the second week of treatment. SBP remained significantly lower than in PLA-treated animals for 2 days following administration of the last dose in all TEL treatment groups. No clinical signs of hypotension were noted in any group. These results suggest that treatment with TEL at a total daily dose of 1-3 mg/kg - administered as a single dose, or split into two equal doses administered 12 h apart - results in a significant, relatively long-lasting reduction of SBP in clinically normal cats. TEL appears to be well tolerated by normal cats at the dosages tested.

Relationship between indirect blood pressure and various stages of chronic kidney disease in cats.

Chronic kidney disease (CKD) is a common cause of secondary systemic hypertension in cats. We investigated the relationship between indirect blood pressure and the prevalence of systemic hypertension in various CKD stages in cats. Client-owned cats (24 control cats and 77 cats with CKD) were included. Biochemical examinations of plasma were conducted by a commercial laboratory. Diseased cats were divided into two groups based on the International Renal Interest Society (IRIS) guidelines (II and III–IV). Indirect blood pressure was measured using an oscillometric technique. Severe hypertension was diagnosed if systolic blood pressure (SBP) was ≥180 mmHg. Indirect blood pressures were significantly higher in IRIS stage III–IV than in the control cats. Of 77 cats with CKD, 25 (32.5%) had severe hypertension. The frequency of severe hypertension increased with an increase in IRIS stage; 0% in the controls, 27.6% in the IRIS stage II, and 47.4% in the IRIS stage III–IV, respectively. The indirect SBP was weakly correlated with urea nitrogen (r=0.27) and creatinine (r=0.23) concentrations in plasma. Binary logistic regression analysis showed that if plasma creatinine concentration is >3.7 mg/dl, cats with CKD had an increased risk for developing severe hypertension (P<0.001). Our results suggest that indirect blood pressure was correlated with the severity of CKD, and the prevalence of severe hypertension increased in cats with severe CKD. The risk of severe hypertension may be high in cats with severe CKD.

Anaesthesia with sevoflurane in pigeons: minimal anaesthetic concentration (MAC) determination and investigation of cardiorespiratory variables at 1 MAC

The objective of the study was to determine the minimal anaesthetic concentration (MAC) of sevoflurane (SEVO) in pigeons and investigate the effects of 1 MAC SEVO anaesthesia on cardiovascular and...

Blood Pressure Estimation Accoording to Photoplethysmographic Signal Steepness

Abstract. The purpose of this paper is to prove the assumption that there is a correlation between the systolic blood pressure and the photoplethysmographic signal steepness. A method for indirect systolic blood pressure estimation based on photoplethysmographic signal steepness is proposed in this paper. Method: It is proved that based on Hooke’s law, the steepness of pressure and volume (diameter) of pulse waves differ by a constant. The coefficient for calculating arterial blood pressure when volume pulse wave steepness is known is presented in this paper. The Windkessel model is selected for the modeling. Experimental evaluation is based on veloergometrical trials. Volume pulse wave was obtained using a photoplethysmography device that is put on a finger. Blood pressure was measured using a semi-automatic OMRON blood pressure monitor. Results: The simulation of an arterial system using the Windkessel model shows that the steepness of pressure and volume pulse waves correlate. Ten veloergometrical trials were performed during the experimental evaluation. A significant 0.855±0.025 (p &lt; 0.001) correlation between the photoplethysmographic signal steepness and the systolic blood pressure was obtained. The calculated and measured blood pressure values vary no more than ±5mmHg. Conclusions: The results demonstrate that the photoplethysmographic signal wavefront can be successfully applied in wearable devices that can be used for constant 24 hour registration of blood pressure for both home use and clinical practice.DOI: http://dx.doi.org/10.5755/j01.itc.44.4.12562

Computed tomography angiography of coarctation of the aorta in a dog

Coarctation of the aorta has been described previously as either a post-mortem or angiographic finding in three dogs with clinical signs related to the aortic coarctation. A 10-year-old dog was presented for evaluation of suspected laryngeal paralysis. On physical examination, femoral pulses were absent bilaterally, with an indirect systolic blood pressure difference of 60 mmHg between the ipsilateral thoracic and pelvic limbs. Coarctation of the aorta was detected on a thoracic computed tomographic angiography study. The coarctation was pre-ductal in position, with extensive dilation of the descending thoracic aorta. Characteristic rib changes that are seen in humans with coarctation were not apparent in this dog. 3D reconstructions of the thorax provided high vascular definition with exact localization of the aortic narrowing.

PHYSIOLOGIC AND SERUM BIOCHEMISTRY VALUES IN FREE-RANGING HOFFMANN'S TWO-TOED (CHOLOEPUS HOFFMANNI) AND BROWN-THROATED THREE-TOED (BRADYPUS VARIEGATUS) SLOTHS IMMOBILIZED USING DEXMEDETOMIDINE AND KETAMINE

Dexmedetomidine, a highly selective alpha-2 adrenergic agonist and dextrorotary enantiomer of medetomidine, was combined with ketamine and used to immobilize 14 free-ranging Choloepus hoffmanni (Hoffmann's two-toed sloths) and 11 Bradypus variegatus (brown-throated three-toed sloths) in Upala, Costa Rica. Following intramuscular injection of ketamine (2.1 mg/kg) and dexmedetomidine (11 microg/kg), heart rate, respiratory rate, and indirect systolic blood pressure were measured every 5 min for a total of 25 min. An iStat (CG8+) was used to evaluate serum biochemical and hematologic values during anesthesia. After 30 min of anesthesia, atipamezole (0.13 mg/kg) was administered intramuscularly, which resulted in rapid and smooth recoveries. Mean heart rate and respiratory rate remained unchanged in both C. hoffmanni and B. variegatus over time. Progressive decreases in mean indirect systolic blood pressure were documented in both species. Results of this study suggest a combination of dexmedetomidne and ketamine is a safe and effective anesthetic protocol for use in free-ranging C. hoffmanni and B. variegatus. Similar to other alpha-2 adrenergic agonist-based immobilization protocols, close monitoring of cardiovascular and respiratory parameters are recommended. This study also provides serum biochemical and hematologic data in free-ranging C. hoffmanni and B. variegatus.

Preliminary pharmacokinetics and cardiovascular effects of fenoldopam continuous rate infusion in six healthy dogs

Fenoldopam is a selective dopamine-1 receptor agonist that causes peripheral arterial vasodilation, increased renal blood flow, and diuresis. Enthusiasm exists for the use of fenoldopam in nonpolyuric kidney injury in dogs, although pharmacokinetic data are lacking. The purpose of this study was to collect basic pharmacokinetic and hemodynamic effect data for fenoldopam when administered to healthy awake dogs. Six healthy, awake beagles were given a 180-min fenoldopam constant rate infusion at 0.8 μg/kg per minute followed by a 120-min washout period. Citrated blood was collected during and after infusion for the measurement of plasma fenoldopam concentration by HPLC with mass spectrometry. Heart rate and indirect systolic blood pressure were concurrently measured. Mean ± SD, steady-state plasma fenoldopam concentrations of 20 ± 17 ng/mL were achieved within 10 min of starting the infusion. Area under the plasma concentration-time curve was 3678 ± 3030 ng/mL · min, and plasma clearance was 66 ± 43 mL/min per kg. Elimination was rapidly achieved in all dogs. Heart rate and systolic blood pressure were unaffected by the fenoldopam infusion. Based on the results of this study, further evaluation of the effects of fenoldopam in dogs at differing doses and in dogs with clinical conditions such as acute nonpolyuric kidney injury is warranted.

Three-quarters nephrectomy in rats as a model of early renal failure.

To produce a compatible model of early renal failure easily, we prepared three-quarters nephrectomized animal. 20 Sprague-Dawley rats were divided into the following two groups: 10 rats which received three-quarters nephrectomy (Nx group), assuming the weight of both kidneys to be equal, and another 10 rats which underwent sham operations (S group). The levels of creatinine clearance in Nx group and S group were 286.5 +/- 33.5 vs. 431.1 +/- 55.9 microliters/min/100 g BW (P less than 0.001) on week 2, and 233.0 +/- 16.7 vs. 562.3 +/- 62.9 microliters/min/100 g BW (P less than 0.001) on week 10, respectively. The indirect and direct systolic blood pressure (SBP) values of Nx group and S group at the 10th week were 154.5 +/- 5.5 vs. 131.1 +/- 3.6 mmHg (P less than 0.01), and 148.2 +/- 4.8 vs. 130.7 +/- 6.6 mmHg (P less than 0.01), respectively. Significant changes in the levels of urinary protein excretion, urinary sodium output, urinary epinephrine, urinary norepinephrine and plasma renin activity between both groups were recognized on the 10th week. The planar area of Nx group was significantly increased as compared to that of S group (11.0 +/- 0.3 vs. 7.2 +/- 0.1 x 10(-3) mm2, P less than 0.001). It is concluded that this model resembles early renal failure in humans because slow progression of renal dysfunction occurred with mild elevation of SBP, and that it is adequate for evaluating the influence of glomerular hypertrophy, resulting in glomerulosclerosis.

IMMOBILIZATION OF FREE-RANGING HOFFMANN'S TWO-TOED AND BROWN-THROATED THREE-TOED SLOTHS USING KETAMINE AND MEDETOMIDINE: A COMPARASION OF PHYSIOLOGIC PARAMETERS

Free-ranging Hoffmann's two-toed sloths (Choloepus hoffmanni; n=26) and brown-throated three-toed sloths (Bradypus variegatus; n=15) were manually captured and immobilized with 2.5 mg/kg ketamine + 0.02 mg/kg medetomidine administered intramuscularly. Physical examinations were conducted on each sloth 10 min after initial injection, and blood, fecal, and ectoparasite samples were collected. Heart rate, respiratory rate, body temperature, indirect systolic blood pressure, and indirect peripheral oxygen saturation were monitored every 5 min for the duration of anesthesia. After 45 min, atipamazole (0.1 mg/kg) was administered intramuscularly, as an antagonist to medetomidine, in order to facilitate recovery. All recoveries were smooth, rapid, and uneventful. Physiologic parameters were compared across time, gender, and species. All sloths, regardless of species and gender, demonstrated a time-dependent decrease in heart rate and blood pressure, and an increase in respiratory rate, during the course of anesthesia. Peripheral oxygen saturation was similar for all sloths over time. There were significant species differences for heart rate (Choloepus > Bradypus), respiratory rate (Choloepus > Bradypus), and systolic blood pressure (Bradypus > Choloepus), while there were significant gender differences for body temperature (males > females) and blood pressure (males > females). Results of this study suggest that the ketamine-medetomidine mixture, as described above, is a safe and effective anesthetic combination in free-ranging two- and three-toed sloths, although peripheral blood pressure should be monitored during anesthesia.

Normotensive menopausal rats: Effects of Enalapril on Sexual Hormones and on Nitric Oxide System Activity in the Kidney, Heart and Aorta

Studies in animal models suggest that sexual hormones, oxidative stress, and impaired nitric oxide (NO) system and renin‐angiotesin system activation play a role in hypertension during menopause. However, the involved mechanisms are still unknown.Objective: To evaluate the effects of enalapril, an inhibitor of the angiotesin‐converting enzyme (ACE), on systolic blood pressure (SBP), sexual hormones and NO syntase (NOS) activity in normotensive menopausal rats.Wistar rats were ovariectomized, and ten weeks later were divided into two groups: Experimental (E) treated with enalapril for 30 days (15 mg/Kg/day) and Control (C) with tap water. We measured: indirect SBP, androgen, estradiol and FSH plasma levels, and NOS activity (14C‐arginine) in the kidney, aorta and heart at the end of treatment.Results: treatment with enalapril did not induce any changes in SBP, estradiol, androgen and FSH plasma levels.NOS activity (pmol/min 100g tissue), * p&lt;0.01 vs ControlConclusions: The ACE inhibition did not modify SBP or sexual hormones in normotensive menopause rats, but treatment with enalapril improved NOS activity significantly in all the studied tissues. This fact could improve renal and cardiovascular function during menopause.

Renal and Vascular Nitric Oxide System in Reduced Renal Mass Saline Hypertension

Background: Reduction in renal mass is associated with several structural and functional adaptations including compensatory renal growth and hemodynamic changes. The mediators of the renal hemodynamic adaptations have not been definitively identified. Several investigators have postulated that nitric oxide (NO) is involved this physiological mechanisms. The purpose of this study was to evaluate the role of vascular and renal NO pathway in the model of subtotal nephrectomy-salt load hypertension. Materials and Methods: Wistar rats with 75% renal mass reduction (RMR) and saline load were studied during 4 weeks. Weekly, indirect systolic blood pressure (SBP) were measured. One week after nephrectomy, animals were divided in two groups, hypertensive (SBP > 140 mm Hg) and normotensive (SBP < 140 mm Hg). Urinary excretion of nitrates and nitrites (NOx), urinary chemioluminiscence levels and NOS activity in the left kidney and in the thoracic aorta artery were determined at the fourth week after subtotal nephrectomy. Results: Urinary excretion of sodium was higher in normotensive rats than hypertensive rats and in both groups this parameter was higher than in sham rats. NOx excretion and NOS activity in the different nephron segments were higher in normotensive rats than in the hypertensive ones. In contrast, NOS activity in aorta sections and urinary chemiluminescence levels in hypertensive animals were enhanced compared with normotensive rats. These parameters were higher in both groups of nephrectomized rats than in sham ones. Conclusion: This study provides evidence to support the fact that the activation of the renal NO system is an important mechanism whereby the remnant kidney regulates sodium and water balance, contributing to control the arterial blood pressure in the renal mass reduction and saline load model.

The Normal Difference in Bilateral Indirect Blood Pressure Recordings in Hypertensive Individuals

Abstract. Objective: If there is a significant dichotomy between bilateral systolic blood pressure determinations in both arms in hypertensive individuals, it is often taken as a sign of underlying pathology. The primary objective was to determine what the normal variation might be for a significant difference between blood pressures in both arms. A clinically significant difference was chosen as a systolic blood pressure value greater than 10 mm Hg between the upper extremities, as is commonly quoted at the bedside and in the literature. Methods: Bilateral indirect blood pressure determinations were obtained in 100 subjects with hypertension in the sitting position. The blood pressure was obtained by two observers, one the recorder and the other who obtained the blood pressure but was blinded to the actual values taken. The order of blood pressure determination in the first arm was determined prior to the study from a table of random numbers. The coefficient of variation in obtaining the blood pressure in each arm was determined in 5 of the 100 subjects. The age, sex, and handedness of each individual were recorded as demographic variables. Results: The average left and right systolic blood pressures were 139 ± 22 and 141 ± 22 mm Hg, respectively. The average left and right diastolic blood pressures were 78 ± 12 and 79 ± 13 mm Hg, respectively. There was no significant difference between left minus right systolic or diastolic differences (paired t‐test). There was no significant difference between systolic or diastolic blood pressures between gender or between left‐ and right‐handed individuals (nonpaired t‐test). The average coefficients of variation for taking right and left arm systolic pressures were 2.90% and 1.32%, respectively. Eighteen subjects (18%) had differences in systolic blood pressure between both arms exceeding 10 mm Hg (10% to 26%, 95% confidence interval). Conclusions: Differences of more than 10 mm Hg in indirect systolic blood pressure recordings between arms are frequent in asymptomatic hypertensive individuals and do not per se indicate any pathologic condition. In the right clinical situation, differences that are noted should be repeated and should be added to the total clinical picture when used to determine whether a pathologic condition is present. Assuming no significant aortic or subclavian disease in the population tested, the specificity of the bilateral blood pressure test was 82%.

Mice lacking inducible nitric oxide synthase develop spontaneous hypercholesterolaemia and aortic atheromas

Nitric oxide (NO) has been implicated in various aspects of the atherogenic process and has been shown to possess both protective and cytotoxic properties. Recently, increased expression of inducible nitric oxide synthase (iNOS) has been detected in atherosclerotic lesions, although there is no consensus as to its pathogenetic significance [1,2]. In this longitudinal study we show that iNOS plays an important protective role in the atherogenic process. Indirect systolic blood pressure was measured by photoplethysmography in unanesthetized mice fed either a basal or high salt diet, and found to be significantly higher in iNOS-deficient mice than in wild type controls at three months of age ( P=0.038 (basal diet) and P=0.0005 (high salt diet)). In addition, relative to controls, the iNOS-deficient mice had significantly elevated serum cholesterol levels at 3, 9 and 12 months of age ( P=0.0017, 0.0001 and 0.0002 for the respective ages) as well as a significantly higher incidence of atherosclerotic plaques. These findings suggest that iNOS targeted mutant mice, historically used as an animal model to investigate the role of nitric oxide in the inflammatory response [3,4], may also serve as a model for the study of cholesterol homeostasis and atherogenesis.

Genetic mapping of blood pressure quantitative trait loci in Milan hypertensive rats.

In a previous study, by using a candidate gene approach, we detected in both Milan hypertensive rats and humans a polymorphism in the alpha-adducin gene (ADD1) that was associated with blood pressure and renal sodium handling. In the present study, a genomewide search with 264 informative markers was undertaken in 251 (Milan hypertensive strain x Milan normotensive strain) F2 rats to further investigate the contribution of the adducin gene family (Add1, Add2, and Add3) and to identify novel quantitative trait loci (QTLs) that affect blood pressure. The influence of 2 different methods of blood pressure measurement, the intracarotid catheter and the tail-cuff method, was also evaluated. We found evidence that QTLs affected systolic blood pressure (SBP) measured at the carotid (direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chromosome 14 on Add1 locus (LOD=3.2). A QTL for SBP measured at the tail (indirect SBP) was found on rat chromosome 10 around D10Rat33 (LOD=5.0). All of these QTLs identified chromosomal regions not detected in other rat studies and harbor genes (Na(+)/H(+) exchanger A3; alpha-adducin; alpha(1B)-adrenergic receptor) that may be involved in blood pressure regulation. Therefore, these findings may be relevant to human hypertension, also in consideration of the biochemical and pathophysiological similarities between MHS and a subgroup of patients of primary hypertension, which led to the identification of alpha-adducin as a candidate gene in both species.

Differential Regulation of the Sodium Pump α-Subunit Isoform Gene by Ouabain and Digoxin in Tissues of Rats

The effects of ouabain and digoxin on both the systolic blood pressure (SBP) and sodium pump alpha-subunit expression in some tissues of rats were compared. Normal rats were injected with ouabain, digoxin, and normal saline (NS), respectively, everyday, and indirect SBP was recorded once a week. Six weeks later, all the rats were killed, and sodium pump alpha1-, alpha2-, and alpha3-subunit mRNA levels were detected in the myocardium, kidney, adrenal gland, aortic smooth muscle, and hypothalamus by the RT-PCR method. The results showed that the SBP of rats infused with ouabain increased significantly at the end of week 6, while no difference in SBP was found between the digoxin and NS groups. The effects of ouabain and digoxin on sodium pump alpha-subunit isoform expression were also different. Myocardium: both ouabain and digoxin stimulated expression of the alpha3-isoform whereas alpha2 was unchanged. Levels of the alpha1 isoform decreased significantly in the ouabain group and decreased slightly in the digoxin group, respectively. Kidney: digoxin had the same effects as ouabain. alpha1 levels increased, but those of alpha2 and alpha3 remained unchanged. Adrenal gland: alpha2 and alpha3 levels increased, but those of alpha1 decreased in the ouabain group. alpha1 and alpha3 levels increased and those of alpha2 remained unchanged in the digoxin group. Aortic smooth muscle: both ouabain and digoxin increased alpha1 and alpha3 expression. alpha2 levels decreased in the digoxin group but remained unchanged in the ouabain group. Hypothalamus: both ouabain and digoxin stimulated alpha1 expression, while alpha2 and alpha3 levels remained unchanged. The results of this study have shown that ouabain and digoxin have the different effects on both the systolic blood pressure and expression of sodium pump alpha-subunit isoforms in some tissues in rats. Further studies on the expression of sodium pump alpha-subunit isoforms might be helpful for the understanding of the physiological role of endogenous ouabain and the molecular mechanisms involved in the pathogenesis of hypertension.

Cardiovascular effects ofArbutus unedo L. in spontaneously hypertensive rats

In order to examine the effect of Arbutus unedo extract on the development of genetic hypertension, three groups of six male spontaneously hypertensive rats (SHR) from 4 to 10 weeks of age, received orally an aqueous extract of the root of this Ericaceae plant at doses of 5, 50 and 250 mg/kg/24 h. The fourth group (n = 6) received tap water only and served as a control. A significant (p < 0.01) reduction of indirect systolic blood pressure (BP) was observed after 4 weeks of treatment with the two highest doses but this effect attenuated 2 weeks later. The continuous measurement of direct BP in conscious 10-week-old rats indicated that chronic treatment with Arbutus did not significantly alter the BP level, the heart rate (HR), the cardiac baroreflex sensitivity and the sympathetic nervous and renin– angiotensin system activities. In contrast, Arbutus (50 mg/kg/24 h) attenuated the pressor responses to phenylephrine and angiotensin I. Finally, a diuretic effect was evidenced in the group receiving the highest dose. It is concluded that chronic oral administration of Arbutus unedo slowly delayed the development of hypertension but did not alter the final level of BP and HR in the SHR. The vascular and renal effects of this plant, which may account for its use in folk medicine, require a more detailed analysis. © 1998 John Wiley & Sons, Ltd.