Mohammed O. Hassan

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans.

To determine whether venous plasma norepinephrine concentrations consistently reflect changes in sympathetic nervous activity, the influence of mental arithmetic, static handgrip, and submaximal bicycle exercise on intra-arterial blood pressure, heart rate, and plasma norepinephrine was studied in 51 subjects with untreated essential hypertension (mean age, 46 years; range, 16-69 years). At rest, plasma norepinephrine was unrelated to age or blood pressure. Mental arithmetic increased mean arterial pressure from 108 +/- 18 to 127 +/- 18 mm Hg (mean +/- S.D.; p less than 0.001) and heart rate from 69 +/- 7 to 93 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (547 +/- 297 to 518 +/- 250 pg/ml). Isometric exercise raised mean arterial pressure from 115 +/- 18 to 148 +/- 21 mm Hg (p less than 0.001) and heart rate from 76 +/- 9 to 95 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (683 +/- 253 to 741 +/- 253 pg/ml). Bicycle exercise increased mean arterial pressure from 114 +/- 20 to 146 +/- 26 mm Hg (p less than 0.001), heart rate from 77 +/- 9 to 128 +/- 19 beats/min (p less than 0.001), and plasma norepinephrine from 645 +/- 228 to 1151 +/- 462 pg/ml (p less than 0.001). Both the maximum mean arterial pressure and the peak heart rate attained during bicycle exercise were related to the exercise plasma norepinephrine level (r = 0.33, p less than 0.02 and r = 0.28, p less than 0.03, respectively). Increases in plasma norepinephrine with exercise were not greater in older or more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Heritability of Determinants of the Metabolic Syndrome among Healthy Arabs of the Oman Family Study

The metabolic syndrome, as defined by the International Diabetes Federation, was investigated in five large, extended, highly consanguineous, healthy Omani Arab families of a total of 1277 individuals. Heritability (h2) of the phenotypic abnormalities that make up the syndrome and other related traits was estimated by variance decomposition method using SOLAR software. The overall prevalence of the syndrome was 23%. The prevalence of abnormalities making the syndrome in a descending order were: obligatory waist circumference, hypertension, raised fasting blood glucose, low serum high‐density lipoprotein (HDL), and raised serum triglycerides (TGs). Highly significant, but widely spread, h2 values were obtained for: height (0.68), weight (0.68), BMI (0.68), serum HDL (0.63), serum leptin (0.55), percentage body fat (0.53), total serum cholesterol (0.53), fasting serum insulin (0.51), homeostasis model assessment‐insulin resistance index (0.48), serum TG (0.43), waist circumference (0.40), diastolic blood pressure (0.38), and 2‐hour glucose level (0.17), whereas for the metabolic syndrome itself, h2 was 0.38. The wide spread of h2 results (0.07 to 0.68) indicates that some determinants, such as weight, BMI, and HDL level, are under significant genetic influence among the Omani Arabs. Other determinants such as insulin resistance, abdominal obesity, diastolic blood pressure, and TG levels seem to be more environmentally driven.

Pressor responses to laboratory stresses and daytime blood pressure variability.

We studied 56 patients with essential hypertension to determine whether responses to standardized laboratory mental and physical challenges accurately reflect blood pressure variability during routine daily activities. Four activities were performed in the laboratory: mental arithmetic, a reaction time test, isometric exercise, and submaximal bicycle exercise. Blood pressure was measured directly from a brachial artery catheter. We then recorded intra-arterial ambulatory blood pressure away from hospital over 24 h. A frequency histogram was constructed from all cardiac cycles when subjects were awake. Variability of ambulatory blood pressure was defined as the standard deviation about the mean waking value. The increase in mean arterial pressure (MAP) during each of these four challenges correlated significantly with the variability of mean arterial pressure (highest correlation: reaction time test, r = 0.53, P less than 0.00001; lowest correlation: mental arithmetic, r = 0.26, P less than 0.03), and five subjects who were highly reactive to all four challenges also demonstrated increased blood pressure variability. We therefore conclude that these commonly used laboratory tests can give some information about the behaviour of blood pressure in daily life in some subjects, but overall the variance in blood pressure variability that can be accounted for by the pressor response to these standardized challenges is low.

Exercise training attenuates ageing-induced BKCa channel downregulation in rat coronary arteries.

Physical inactivity and ageing are widely recognized as risk factors for development of coronary artery disease. One of the characteristic changes that occurs in aged coronary artery is downregulation of their large‐conductance voltage‐ and calcium‐activated K+ (BKCa) channels. In this study, we investigated the effects of moderate exercise training (ET) on the activity of BKCa channels in coronary arteries of aged rats. Old Fischer 344 rats (23–26 months old) were randomly assigned to sedentary (O‐SED, n= 24) or exercise‐trained groups (O‐ET, n= 28). The O‐ET rats underwent a progressive treadmill exercise‐training programme for 60 min day−1, 5 days week−1 for 12 weeks. Young animals were used for comparison. Coronary arteries were mounted on a wire myograph, and contractions in response to 1, 10, 30, 50 and 100 nmol l−1 iberiotoxin were compared. Iberiotoxin (100 nmol l−1) contracted coronary arteries of young, O‐SED and O‐ET rats by 115 ± 14, 36 ± 5.6 and 61 ± 5% of 5‐hydroxytryptamine‐induced contractions, respectively. Patch‐clamp studies revealed a larger magnitude of BKCa current in young (104 ± 15.6 pA pF−1) compared with O‐ET (44 ± 9 pA pF−1) and least in O‐SED coronary smooth muscle cells (8.6 ± 2 pA pF−1). Western immunoblotting was performed to study expression levels of BKCa channel proteins. The α and β1 subunits of the BKCa channel were reduced by 40 ± 3.5 and 30 ± 2.6%, respectively, in coronary arteries of old compared with young rats, and ET attenuated this reduction in expression level to 28 ± 2 and 12 ± 4%, respectively. Our results showed that ageing was associated with a reduction in BKCa channels, and ET partly reversed this reduction. We conclude that low‐intensity ET may be beneficial in restoring age‐related decline in coronary vasodilatory properties mediated by BKCa channels.

Insertion-Deletion Polymorphism in the Angiotensin-Converting Enzyme (ACE) Gene Among Sudanese, Somalis, Emiratis, and Omanis

ABSTRACT The angiotensin-converting enzyme (ACE) gene in humans contains an insertion-deletion polymorphism in its intron 16. Because of its involvement with the renin-angiotensin system, the insertion-deletion polymorphism of the ACE gene has been widely investigated in different populations and in case-control studies. However, similar studies for Arab populations are limited in number. Therefore we have investigated the frequencies of the *I and *D alleles of the ACE gene among Sudanese, Somalis, and Arab nationals of the United Arab Emirates and Oman using previously described methods. Our data indicate a preponderance of the *D allele among the Arab and African populations studied (Sudanese, 0.64; Somalis, 0.73; Emiratis, 0.61; and Omanis, 0.71).

Subband decomposition soft-decision algorithm for heart rate variability analysis in patients with obstructive sleep apnea and normal controls

A new method for screening of obstructive sleep apnea (OSA) is investigated. This method is based on the estimation of the energy distribution of the R-R interval (RRI) signals in the time domain. The novelty of the technique arises from the implementation of the soft-decision algorithm of subband decomposition. This soft-decision algorithm will help in finding the ratio of energy (power spectral density (PSD)) in the different frequency bands of the RRI spectrum without implementing any transform technique. Two different ratios--low-frequency/very low-frequency (LF/VLF) and low-frequency/high-frequency (LF/HF)--are used for screening normal and apnea cases. The algorithm can be implemented directly on the (RRI) raw-data or after some pre-processing and filtering steps. The training data used in this study are drawn from the MIT-trial database, while the test data are drawn from the MIT-challenge (chal) database as well as from the sleep disorders laboratory of Sultan Qaboos University (SQU) hospital. Threshold values to identify normal and OSA cases are selected using the receiver operating characteristics (ROC) on the training data. These threshold values are then used for the screening of the test data. The best classification accuracy obtained with the test data (MIT-chal and SQU data) approaches 93% using the LF/VLF ratio. In this case, the sensitivities obtained with MIT-chal and SQU data are 95% and 100%, respectively, while the specificities are 90% and 86% for the same two groups of data.

Long-term exercise training and angiotensin-converting enzyme inhibition differentially enhance myocardial capillarization in the spontaneously hypertensive rat

Objectives To investigate whether combined treatment with lisinopril, an angiotensin-converting enzyme (ACE) inhibitor and exercise training would have an additive effect in enhancing the capillary supply of the left ventricular (LV) myocardium in spontaneously hypertensive rats (SHR). Design Twelve-week-old male SHR were divided into four groups (10–12 each): sedentary, sedentary treated with lisinopril (15–20 mg/kg per day by gavage), exercise trained, and exercise trained while treated with lisinopril. Exercise training consisted of 1 h a day/5 days a week of running on a treadmill. Methods After 10 weeks of experimental protocols, capillary surface density and length density were sterologically determined in 1 μm thick LV tissue samples from perfuse-fixed hearts. Results Lisinopril significantly reduced systolic blood pressure (SBP) and LV mass in the sedentary with lisinopril and exercise trained with lisinopril groups but did not affect the heart rate (HR). Exercise training did not reduce SBP or LV mass, but significantly reduced HR in the exercise trained and exercise trained with lisinopril groups. Lisinopril treatment (sedentary with lisinopril), exercise training (exercise) and their combination (exercise trained with lisinopril) significantly increased myocardial capillary surface area density by 26, 38 and 65% and length density by 38, 48 and 67%, respectively. Conclusion Lisinopril administration and exercise training independently enhanced myocardial capillarization through a reduction of myocardial mass and stimulation of angiogenesis, respectively. A combination of the two treatments enhanced myocardial capillarization more than either intervention alone. This may aid in the restoration of the normal nutritional status of cardiac myocytes compromised by the hypertrophic state of hypertension.

Non-dipping blood pressure in the metabolic syndrome among Arabs of the Oman family study.

Objective: The objective was to examine the circadian changes in blood pressure and their relation to the metabolic syndrome and its components in Omani Arabs.

Baroreflex sensitivity and the blood pressure response to β-blockade

The objective of this analysis was to determine whether changes in baroreflex sensitivity (BRS) within 35 hypertensive patients (25 M, 10 F, mean age 47 years) treated with β-blockade as monotherapy relate to reductions in ambulatory blood pressure (BP) or its variability. BP was recorded intra-arterially directly from the brachial artery before and during submaximal exercise. BRS was determined by the phenylephrine injection technique. MAP and its variability were determined for the awake period of 24-h BP monitoring. Subjects were randomised to one of atenolol, metoprolol, pindolol, or propranolol, and restudied after a mean of 5 months. β-blockade increased BRS in 24 patients and decreased BRS in 11. BRS increased from 6.53 ± 4.94 to 9.40 ± 8.62 ms/mm Hg (mean ± s.d.) (P < 0.01). waking ambulatory map decreased from 125.8 ± 15.8 to 106.4 ± 16.2 mm hg (P < 0.0001), but its variability did not change. higher brs after chronic β]-blockade was associated with a decrease in waking ambulatory map (r = −0.55, P < 0.001), but not with its variability (r = − 0.08). β-blockade attenuated the pressor response to exercise, but there was a positive relationship between the effect of β-blockade on BRS, and on the rise in systolic BP during bicycling (r = 0.63; P < 0.001). any dampening effect of β-blockade on bp variability at rest in hypertensive patients with the greatest increase in brs may be offset by increased pressor responses to physical activity such as exercise. consequently, bp variability is unaffected, even though reductions in ambulatory bp during chronic β-blockade are inversely related to changes in brs. bp responses to β-blockade may be a function of the action of this class of drugs on brs. however, there is considerable variation, between subjects, in their effect on brs. this may have implications for other conditions, such as dilated cardiomyopathy, or following myocardial infarction, in which improvement in brs is one mechanism by which β-adrenoceptor blockade could improve survival.

Effects of overweight and leisure-time activities on aerobic fitness in urban and rural adolescents.

BACKGROUND The aim of this research was to study the effects of overweight and leisure-time activities on maximal aerobic capacity (VO(2)max) in urban and rural Omani adolescents. METHODS A total of 529 (245 males, 284 females) adolescents, aged 15-16 years were randomly selected from segregated urban and rural schools. Maximal aerobic capacity was estimated using the multistage 20-meter shuttle-run test. RESULTS The body mass index (BMI) of urban boys and girls was significantly higher than that of rural boys and girls. Urban boys and girls spent significantly less weekly hours on sports activities and significantly more weekly hours on TV/computer games than their rural counterpart. Urban boys and girls achieved significantly less VO(2)max than rural boys and girls (44.2 and 33.0 vs. 48.3 and 38.6 mL/kg/min, respectively). Maximal aerobic capacity was negatively correlated with BMI in urban boys. CONCLUSION Overweight and inactivity had significant negative effects on cardiorespiratory fitness in urban boys and girls as compared to their rural counterparts. Weight gain in adolescence requires early intervention.