PubMed Health⌕ Search

Biomedical subjects

P R Howe

Publications and source records attributed to P R Howe.

At least 37 records · Page 2Linked to original sources
PubMed1994

Sodium transport activity in cheek epithelial cells from adolescents at increased risk of hypertension.

Sodium transport including amiloride-sensitive Na+/H+ antiporter activity was measured in cheek epithelial cells of adolescents displaying either high or low BP tracking characteristics and in a subgroup of high BP tracking adolescents exhibiting a positive family history of hypertension. From the BP tracking behaviour of over 500 adolescents measured over a period of three years, 24 low BP tracking and 29 high BP tracking adolescents were recruited for the study. Cheek cells were collected from these subjects and proton-dependent, amiloride-sensitive Na+/H+ antiporter activity and the response of this antiporter to a proton gradient were measured. Cheek cell Na+/H+ antiporter activity was 50% lower (P = 0.0004) in the high BP tracking group (1.02 +/- 0.15 nmol Na+/mg protein/5 min (mean +/- SEM) compared with the activity in the low BP tracking group (2.05 +/- 0.24). A significantly lower Na+/H+ antiporter activity (69%; P < 0.01) was also apparent in the high BP tracking adolescents with family history of hypertension (n = 7) compared with the low BP tracking group. The graded response of cheek cell Na+/H+ antiporter activity to the proton gradient was 58% lower (P = 0.0039) for adolescents in the high BP tracking group compared with the low BP tracking group. Passive Na+ influx was also significantly lower in the cheek cells of the high BP tracking group. Our results therefore show that the activity of the Na+/H+ antiporter in cheek cells and the passive Na+ transport activity are lower in those adolescents considered at greatest risk of future development of essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effect of sodium restriction and fish oil supplementation on BP and thrombotic risk factors in patients treated with ACE inhibitors.

Effects of dietary sodium restriction combined with fish oil supplementation on BP and related risk factors were assessed in hypertensives treated with angiotensin converting enzyme (ACE) inhibitors. After a four week run-in phase, a six week intervention trial was conducted in which four matched groups of 14 patients, taking either captopril or enalapril, were assigned to one of four dietary treatments: low sodium (80 mmol/day) with fish oil (5 g of omega-3 fatty acids per day); normal sodium (150 mmol/day) with fish oil; low sodium with olive oil; normal sodium with olive oil. All subjects adopted a low sodium diet and adjustments of nutrient intake were made by double-blind administration of sodium and oils in supplementary tablets and capsules. BP fell in all treatment groups during intervention. However, the reduction of SBP was 4.2 mmHg greater in subjects on a low sodium intake than in those taking normal sodium. There were no differences in BP between those taking olive oil and those taking fish oil but plasma triglycerides and serum thromboxane production were reduced by 27% and 51%, respectively in the latter. Thus the antihypertensive effect of ACE inhibitors can be augmented by sodium restriction alone but supplementing the diet with fish oil may yield additional cardiovascular benefits.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Combined effects of dietary fish oil and sodium restriction on blood pressure in enalapril-treated hypertensive rats.

Sodium restriction and fish oil supplementation are effective dietary measures for preventing or treating mild hypertension. However, their usefulness as an adjunct to drug treatment of hypertension requires further evaluation. In the present study, we examined the influence of dietary sodium and fish oil on the antihypertensive effect of the angiotensin converting enzyme (ACE) inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP). Rats were fed experimental diets containing fish oil or olive oil (5% w/w) and low (0.04% w/w) or normal (0.23% w/w) sodium from 1 to 4 months of age. Tail-cuff blood pressure (BP) rose by 8.4 and 4.3 mm Hg/week, respectively, in untreated and enalapril-treated (2.5 mg/kg/day, orally) rats fed the olive oil/normal sodium diet. Feeding fish oil further reduced the rise in enalapril-treated rats to 2.8 mm Hg/week. When sodium intake was also restricted, the BP rise was almost prevented (1.1 mm Hg/week). In older rats with established hypertension, the low sodium/fish oil diet also potentiated the blood pressure reduction by enalapril (tail-cuff BP fell by 61 mm Hg compared to 25 mm Hg with enalapril alone). These observations were confirmed by direct BP recording in conscious rats following the implantation of aortic catheters. Factorial analysis revealed a highly significant antihypertensive effect of fish oil in both young and adult SHRSP receiving enalapril, and a further interactive effect of dietary sodium restriction with fish oil feeding in young rats. The antihypertensive effects of the dietary interventions were associated with further reductions of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Enhanced blood pressure response to dietary salt in elderly women, especially those with small waist: hip ratio.

OBJECTIVE: To determine the blood pressure responses in elderly normotensive men and women to dietary sodium and to the diunsaturated fatty acid dihomogammalinolenic acid (DGLA), which is derived from linoleic acid. DESIGN: Blood pressure responses were assessed in 66 subjects (36 male, 30 female; mean age 65 years) on two diets differing by approximately 70 mmol/day sodium, combined with daily supplements of either 1 g DGLA or 1 g safflower oil, giving a four-group parallel design. After a common period of salt restriction and salt supplementation, two sets of parallel groups continued with either salt or placebo tablets. The study was blinded, except for dietary adjustments based on 24-h urinary sodium excretion values measured once every 2 weeks. Blood pressures were also measured automatically once every 2 weeks. RESULTS: Urinary sodium excretion (sodium intake) correlated significantly with systolic and diastolic blood pressures. A strong interaction with sex (P < 0.001 for systolic blood pressure) reflected greater responsiveness in women to changing sodium intake. A second major determinant of blood pressure responsiveness was the waist: hip ratio, an index of central obesity; this correlation was independent of the initial sodium intake, initial blood pressure or body mass index. The waist: hip ratio was a powerful predictor of blood pressure changes with sodium intake in women only; women with android fat distribution were, similarly to men, less sensitive to dietary sodium. Daily supplements of 1 g DGLA doubled the concentration of DGLA in plasma but did not influence blood pressure. CONCLUSIONS: Among elderly normotensive subjects, women responded to changes in sodium intake with greater changes in blood pressure than men did. Furthermore, this response was strongly related to the gynaecoid distribution of body fat.

8,11,14-Eicosatrienoic Acid↗
PubMed1993

Vasopressin compensates for acute loss of sympathetic pressor tone in spontaneously hypertensive rats.

1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade. 2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR) stroke-prone SHR (SHRSP), normotensive Wistar-Kyoto (WKY), black-hooded Wistar (BHW) and Sprague-Dawley (SD) rats, aged 5-7 weeks and 7-9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra-arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded. 3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats. 4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains. 5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Chronic central administration of enalaprilat lowers blood pressure in stroke-prone spontaneously hypertensive rats.

Earlier studies on the cardiovascular effects of intracerebroventricular (i.c.v.) administration of angiotensin converting enzyme (ACE) inhibitors implicate angiotensin II (AII) present in the central nervous system in the pathogenesis of hypertension. We have now examined whether central AII contributes to the maintenance of established hypertension in adult stroke-prone spontaneously hypertensive rats (SHRSP). The ACE inhibitor, enalaprilat, was infused i.c.v. for two weeks at a rate of 5 micrograms/h via osmotic minipumps. Control rats were either untreated or infused with saline. Mean arterial pressure (MAP), measured via an indwelling catheter, fell within 24 h in the enalaprilat-treated rats and remained at least 30 mmHg lower than in controls. This difference persisted after intravenous (i.v.) administration of a vasopressin (AVP) antagonist but was eliminated by subsequent ganglion blockade with i.v. pentolinium. Without prior administration of the AVP antagonist, however, the reductions of MAP after pentolinium were smaller. The reduction was still attenuated in treated rats compared with controls but there was a significant difference in the residual MAP. Circulating catecholamine levels were reduced by central ACE inhibition. However, pressor responsiveness to i.v. phenylephrine was unaffected. The results suggest that, in SHRSP, central ACE inhibition lowers blood pressure by reducing sympathetic outflow, implying that central AII has a tonic sympathoexcitatory effect in this strain.

Animals↗
PubMed1992

A low-sodium diet supplemented with fish oil lowers blood pressure in the elderly.

OBJECTIVE: To examine effects of dietary fish oil supplementation with sodium restriction on blood pressure in the elderly. DESIGN: In a double-blind dietary intervention lasting 4 weeks, parallel comparisons of blood pressure were made in volunteers assigned to one of four treatment groups: fish oil and low sodium; fish oil and normal sodium; sunflower oil and low sodium; or sunflower oil and normal sodium. SETTING: Subjects lived at home and attended our nutrition research clinic at fortnightly intervals for dietary counselling and blood pressure measurement. PARTICIPANTS: Health volunteers aged 60-80 years were sought by advertisement. A total of 114 men and women were enrolled in two cohorts; 106, with an initial mean blood pressure of 132/77 mmHg, satisfactorily completed the study. INTERVENTION: All subjects adopted a low-sodium diet and dietary changes were effected by double-blind administration of slow-release sodium chloride or placebo tablets, along with capsules containing either fish or sunflower oil. MAIN OUTCOME MEASURE: The primary measure was the within-subject change in blood pressure after 4 weeks of intervention in each dietary treatment group. RESULTS: Urinary sodium excretion in subjects on low-sodium diets decreased whilst potassium excretion was unaffected. Systolic blood pressure (SBP) fell in the group taking sunflower oil with low sodium, but there was only a transient fall in diastolic blood pressure (DBP). In those taking fish oil with normal sodium, the change in blood pressure was not significant, except after adjustment for initial blood pressure and weight changes. When fish oil was combined with low sodium, however, both SBP and DBP were substantially reduced; the reduction in DBP was significantly greater than in the other treatment groups. CONCLUSION: Dietary fish oil and sodium restriction can interact to lower DBP in the elderly.

Aged↗
PubMed1991

Effects of depleting central and peripheral adrenaline stores on blood pressure in stroke-prone spontaneously hypertensive rats.

The potential role of adrenaline, both circulating and in the central nervous system, in the maintenance of high blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). alpha-Monofluoromethyldopa, a long-lasting inhibitor of dopa decarboxylase, was used to induce rapid depletion of central and peripheral catecholamine stores. Subsequent inhibition of phenylethanolamine-N-methyltransferase (PNMT) allowed the gradual restoration of dopamine and noradrenaline but not adrenaline, resulting in a greater relative depletion of adrenaline. Adrenaline was almost totally depleted in the circulation and peripheral tissues. The resting level of blood pressure, however, was unaffected, excepting after administration of a vasopressin (AVP) antagonist. Moreover, there was no reduction in the magnitude of acute pressor responses to electrical stimulation of the rostral ventrolateral medulla oblongata (C1 area), despite extensive loss of adrenaline from the brainstem and spinal cord. The results suggest that adrenaline contributes to the resting level of blood pressure but that its loss can be offset by the pressor activity of AVP. Thus neither central nor peripheral adrenaline stores appear to be essential for the maintenance of hypertension or for centrally-evoked vasoconstriction in adult SHRSP.

Analysis of Variance↗
PubMed1991

Blood pressure reduction by fish oil in adult rats with established hypertension--dependence on sodium intake.

The effects of fish oil combined with dietary sodium restriction on blood pressure and mesenteric vascular resistance were examined in a series of experiments with adult normotensive (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Rats were fed normal or low sodium diets containing fish oil, olive oil or safflower oil. Small but significant reductions of blood pressure (measured directly in conscious rats) were seen in SHRSP but not in WKY after 8 weeks on a fish oil/low sodium diet, compared with rats fed olive or safflower oil diets with normal sodium content. This antihypertensive effect was not dependent on neurally mediated vasoconstriction but was associated with a reduction of basal resistance in the blood-perfused mesenteric artery. Subcutaneous injection of fish oil reduced blood pressure in adult SHRSP on a normal sodium diet. However, there was a further fall in blood pressure when sodium intake was reduced. The results indicate the antihypertensive effect of fish oil can be enhanced by restricting sodium intake.

Animals↗
PubMed1991

Dietary fish oil administration retards the development of hypertension and influences vascular neuroeffector function in the stroke prone spontaneously hypertensive rat (SHRSP).

An influence of fish oils (rich in eicosapentaenoic acid, EPA) in modulating (a) the development of hypertension in the stroke prone spontaneously hypertensive rat (SHRSP) and (b) vascular neuroeffector mechanisms in the SHRSP was explored. Rats (SHRSP) were placed on a series of diets for a period of 13 weeks from 4 weeks of age. The fatty acid composition of the diets was derived from fish oil, olive oil, safflower oil or beef fat. After 13 weeks, rats fed diets containing fish oil (at a total dietary fat level of either 5% or 15%) had mean blood pressures approximately 20-25 mmHg lower than other SHRSP rats maintained on diets containing either olive oil, safflower oil or beef fat. The dietary schedules providing fish oil depressed the contractile responses mediated by sympathetic nerve stimulation in the mesenteric vascular bed preparation. The results suggest that the n-3 polyunsaturated fatty acids retard the development of hypertension in the SHRSP rat and modulate the contractile responses of blood vessels mediated by sympathetic nerves in the isolated perfused mesenteric vascular bed preparation.

Animals↗
PubMed1991

Lack of effect of short-term changes in sodium intake on blood pressure in adolescent schoolchildren.

The relationship between sodium intake and blood pressure in adolescents was examined in a dietary intervention study. One hundred schoolchildren aged 11-14 years and representing the top, middle and bottom deciles of the blood pressure range completed a crossover protocol requiring them to raise and lower their sodium intake for alternate periods of 4 weeks. Blood pressure and urinary sodium excretion were assessed weekly and diet diaries were recorded at the end of each 4-week diet period. Diet-diary analysis confirmed that sodium intake was selectively affected by the intervention. Estimates of average urinary sodium excretion at the end of each diet period differed by more than 80 mmol/day. However, there was no significant change of either systolic or diastolic blood pressure, measured supine in the whole study group, in either sex or in any of the sub-groups, even in those children representing the highest blood pressure decile. Furthermore, the blood pressure changes seen in individuals during the crossover did not correlate with their changes in sodium excretion. This lack of effect of sodium on blood pressure is consistent with other dietary intervention studies in children and supports the hypothesis that the sodium sensitivity of blood pressure is age-related. We conclude that dietary sodium restriction alone has little potential for lowering blood pressure at an early age, even in children with higher than average blood pressure.

Adolescent↗
PubMed1991

Effects of dietary sodium and fish oil on blood pressure development in stroke-prone spontaneously hypertensive rats.

The postulated antihypertensive effect of dietary fish oil and the influence of dietary sodium on this effect were evaluated in young stroke-prone spontaneously hypertensive rats (SHRSP) by direct intra-arterial measurement of blood pressure. Weaning rats were fed synthetic diets containing olive oil or eicosapentaenoic acid-enriched fish oil (5% of dry weight) with normal (0.23%) or high (2.8%) sodium content. Catheters were implanted after 3 months for blood pressure measurement under resting conditions and to sample blood for catecholamine determinations. Effects of fish oil on vascular reactivity were assessed in the in situ blood-perfused mesentery. The overall observation, from a series of experiments, was that feeding diets containing 5% fish oil to young SHRSP resulted in a small but consistent suppression of the development of hypertension. This effect could be counteracted, however, by increasing dietary sodium intake. Observations after ganglion blockade indicate that the antihypertensive effect of fish oil is unlikely to result from a reduction in sympathetic vascular tone.

Animals↗
PubMed1991

Effects of dietary sodium restriction and fish oil supplements on blood pressure in the elderly.

1. The effects on blood pressure of dietary fish oil, sodium restriction and a combination of both strategies were examined in a short-term dietary intervention study of 50 healthy elderly subjects (average age 67 years) with mean initial systolic and diastolic blood pressures of 133 and 77 mmHg, respectively. 2. Subjects were allocated to one of four treatment groups: fish oil with normal sodium, fish oil with low sodium, sunflower oil with normal sodium and sunflower oil with low sodium for 4 weeks. They then crossed over to the alternative sodium treatment for a further 4 weeks whilst remaining on the same oil. 3. The combination of fish oil supplementation with dietary sodium restriction caused significant reductions of blood pressure in the first 4 weeks: systolic blood pressure (SBP) fell by 8.9 mmHg, mean arterial pressure (MAP) by 7.4 mmHg and diastolic blood pressure (DBP) by 6.0 mmHg. 4. Fish oil enhanced the effect of sodium restriction on blood pressure. In the crossover protocol, a change in sodium excretion of 92 mmol/day was accompanied by changes of 6.4, 3.3 and 2.2 mmHg for SBP, MAP and DBP, respectively, in the subjects taking fish oil. However in those taking sunflower oil, blood pressure did not change significantly. 5. The results indicate beneficial interactive effect of dietary fish oil and sodium intake on blood pressure.

Aged↗
PubMed1990

Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease.

Regional loss of immunohistochemically identified neurons in serial sections through the brainstem of 4 patients with idiopathic Parkinson's disease was compared with equivalent sections from 4 age-matched control subjects. In the Parkinson brains, the catecholamine cell groups of the midbrain, pons, and medulla showed variable neuropathological changes. All dopaminergic nuclei were variably affected, but were most severely affected in the caudal, central substantia nigra. The pontine noradrenergic locus ceruleus showed variable degrees of degeneration. There was also a substantial loss of substance P-containing neurons in the pedunculopontine tegmental nucleus. However, the most severely affected cell group in the pons was the serotonin-synthesizing neurons in the median raphe. In the medulla, substantial neuronal loss was found in several diverse cell groups including the adrenaline-synthesizing and neuropeptide Y-containing neurons in the rostral ventrolateral medulla, the serotonin-synthesizing neurons in the raphe obscurus nucleus, the substance P-containing neurons in the lateral reticular formation, as well as the substance P-containing neurons in the dorsal motor vagal nucleus. Lewy bodies were present in immunohistochemically identified neurons in many of these regions, indicating that they were affected directly by the disease process. These widespread but region- and transmitter-specific changes help account for the diversity of motor, cognitive, and autonomic manifestations of Parkinson's disease.

Aged↗
PubMed1990

Dietary sodium loading elevates blood pressure in baroreceptor denervated rats.

We have examined the possibility that defective baroreflex function may contribute to the hypertensive effect of a high dietary sodium intake. In a preliminary study we found that, after interrupting the baroreflex by sino-aortic denervation (SAD), feeding a high-sodium diet to normotensive Wistar/Kyoto rats (WKY) caused their tail-cuff blood pressure to rise to hypertensive levels. In the present study, SAD and sham-operated WKY were fed diets with either a low or a high sodium content. An increase in the sensitivity of blood pressure to sodium after baroreceptor denervation was confirmed by direct measurement of mean arterial pressure (MAP) in conscious rats via indwelling aortic catheters. After 8 weeks the MAP in SAD rats on the high sodium diet was 35 mm Hg higher than in SAD rats on the low sodium diet. Ganglion blockade reduced MAP to a similar level in all treatment groups, but pressor responses to phenylephrine were greater in SAD rats on the high sodium diet, suggesting that the hypertensive effect of sodium in this group might have been due to increased sympathetic vasoconstriction.

Animals↗
PubMed1989

Co-localization of RNAs coding for phenylethanolamine N-methyltransferase and proenkephalin A in bovine and ovine adrenals.

A 29-mer oligodeoxyribonucleotide probe, complementary to the coding region of bovine phenylethanolamine N-methyltransferase (PNMT) mRNA was synthesized. Characterization of this probe by Northern blot hybridization showed that it hybridized to a single band in RNA extracted from bovine and ovine adrenal medullae. The molecular size of this hybridized band was approximately 1.0-1.2 kb which is consistent with recently reported data on the molecular weight of bovine PNMT mRNA. In situ hybridization histochemistry was carried out with this probe on bovine and ovine adrenal sections and results compared on adjacent sections with a probe against proenkephalin A (ProEnk A) mRNA synthesized previously. Both showed a similar localization to the outer margin of cells in the adrenal medulla. The results of this study provide strong evidence at the level of mRNA expression that ProEnk A mRNA is expressed preferentially in the adrenaline synthesizing cells within the adrenal medulla. Further, it demonstrates the usefulness of a synthetic oligodeoxyribonucleotide probe for the study of PNMT gene expression.

Adrenal Medulla↗
PubMed1989

Limited baroreflex control of heart rate in young stroke-prone spontaneously hypertensive rats.

Controversy regarding possible differences of baroreflex gain in spontaneously hypertensive rats (SHR) and their relationship to the rise in blood pressure may be due in part to variations in the methods used to assess baroreflex function. In this study, we have compared the baroreflex control of heart rate in normotensive (Wistar-Kyoto, WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats at 1 and at 7 months of age. Mean arterial pressure and heart rate were monitored in conscious rats following implantation of arterial and venous catheters. Phenylephrine and nitroprusside were given intravenously and the peak responses of mean arterial pressure and heart rate were recorded. In the young rats, these recordings were repeated under anaesthesia. Individual slopes for responses to phenylephrine or nitroprusside were obtained by linear regression. A single relationship covering both sets of responses was also obtained by fitting the data to a sigmoidal curve. The latter approach enabled the baroreflex to be represented as a single function which has a single determinant of gain, operates within defined limits and can be readily related to resting mean arterial pressure and heart rate. This approach demonstrated that: (1) in adult SHRSP, the baroreflex had reset to operate at higher resting levels of mean arterial pressure; (2) the range of heart rate control was smaller in both young and adult SHRSP compared with WKY; (3) average gain was slightly, but not significantly lower in adult SHRSP; (4) anaesthesia reduced heart rate range and average gain in both strains of rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗