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Biomedical subjects

G A MacGregor

Publications and source records attributed to G A MacGregor.

At least 55 records · Page 3Linked to original sources
PubMed1999

Platelet sodium/hydrogen exchanger activity in normotensives and hypertensives.

Increased activity of sodium/hydrogen exchange provides a potentially important mechanism for the development of hypertension. The aims of this study were to compare platelet sodium/hydrogen exchanger activity and renal acid-base excretion in normotensives and hypertensives of Caucasian origin. Platelet intracellular pH (pHi) was measured using the fluorescent dye BCECF to monitor intracellular pH. Sodium/hydrogen exchanger activity was estimated from the recovery of pHi clamped to 6.25 with nigericin. Normotensives had supine blood pressures of < 140 and < 90 mmHg; those with essential hypertension had blood pressures > 150/95 mmHg with no known secondary cause. Measurements of platelet pHi and sodium/hydrogen exchanger activity were made on 26 normotensives (ten female, sixteen male) and 25 hypertensives (five female, twenty male). All subjects were on their usual dietary sodium intake. Statistical analysis was by two-way analysis of variance for gender and blood pressure status. Group values are expressed as means+/-SD and a P value of < 0.05 was taken as being statistically significant. There were no significant differences in platelet pHi between the normotensive (n = 26) and the hypertensive (n = 25) group: pHi 7.21+/-0.14 and 7.18+/-0.16, respectively. The pHi recovery after acidification was sodium-dependent and inhibited by N-hexamethylene amiloride. Comparison of kinetic constants showed no significant differences between the normotensive and the hypertensive groups: values for rate constants and initial velocities were 0.24+/-0.04 s(-1), 0.16+/-0.03 dpHi/s for the normotensives and 0.25+/-0.05 s(-1), 0.16+/-0.03 dpHi/s for the hypertensives, respectively; there were also no significant differences in proton fluxes. The inability to find raised platelet sodium/hydrogen exchanger in the hypertensives contrasts with previous observations using other methods for the measurement of this exchanger in platelets and this raises important methodological issues in the assessment of platelet sodium/hydrogen exchanger activity.

Adult↗
PubMed1999

Relationship between the M235T and G(-6)A polymorphisms of the angiotensinogen gene.

AIMS: Previous studies have reported tight linkage disequilibrium between the T235 and the A(-6) molecular variants of the angiotensinogen gene. This study was designed primarily to ascertain whether a similar relationship exists between the M235 and the G(-6) variants of the gene. We have investigated the degree of agreement between the genotypes of the M235T and the G(-6)A polymorphisms in two ethnic groups. METHODS: Subjects were an heterogeneous group of normotensive and hypertensive subjects of Caucasian (n = 77) and Afro-Caribbean (n = 51) origin. DNA was extracted from whole blood and was genotyped for both the M235T and G(-6)A polymorphisms using PCR-based methods. RESULTS: The distribution frequencies of the MM, MT, and TT genotypes were 0.39, 0.42, and 0.20 in white subjects, and 0.09, 0.17, and 0.74 in black subjects, respectively (chi-square, P < 0.0001). The distribution of AA, GA, and GG genotypes also differed between the two groups as follows: 0.22, 0.48, and 0.30 in white subjects, and 0.82 and 0.18 and 0 in black subjects respectively (chi-square, P < 0.0001). The agreement for TT-AA, MT-GA, and MM-GG was 93%, 91%, and 76% respectively in white and 100%, 67% and 0% respectively in black subjects. CONCLUSIONS: The results indicate ethnic differences in the distribution of both M235T and G(-6)A genotypes. The trend towards a decrease in the degree of agreement in the order of TT-AA > MT-GA > MM-GG suggests that linkage disequilibrium between the M235 and G-6 variant does not mirror that observed with the T235 and A-6 variants. These observations may have significant implications regarding the associations between the G(-6)A polymorphism and hypertension. However, this needs to be further investigated.

Angiotensinogen↗
PubMed1999

Epithelial sodium channel activity is not increased in hypertension in whites.

Abnormal renal sodium transport causing excess reabsorption of sodium may be one mechanism that causes high blood pressure. For example, increased activity of epithelial sodium channels in the distal tubule is the cause of high blood pressure in Liddle's syndrome, a rare familial form of hypertension. We have shown that the increase in sodium channel activity can be detected in the nose using transepithelial potential difference measurements in 1 family with Liddle's syndrome. We therefore used nasal potential difference measurements to look for increased sodium channel activity in white patients with essential hypertension. Transnasal potential difference was measured in 42 white hypertensive (HT) subjects and 38 white normotensive (NT) subjects before and after topical application of 10(-4) mol/L of amiloride. There was no difference in maximum potential between HT and NT subjects (HT, -18.8+/-0.9 mV; NT, -18.2+/-1.0 mV) (values mean+/-SEM; lumen-negative with respect to the submucosa). However, the postamiloride potential was significantly higher (HT, -12.6+/-0.7 mV; NT, -10.5+/-0.7 mV; P=0. 015) and the change in potential in response to amiloride significantly lower (HT, 6.2+/-0.5 mV, 33.1+/-2.0%; NT, 7.7+/-0.6 mV, 41.9+/-2.0%; P=0.046 and 0.003, respectively) in HT than in NT subjects. These results suggest that sodium channel activity is not increased in whites with essential hypertension and indicate that sodium channel overactivity similar to that seen in Liddle's syndrome is unlikely to be the cause of high blood pressure in this group. Increased postamiloride potential may reflect increased activity of chloride channels or amiloride-insensitive sodium channels.

Adult↗
PubMed1999

Structural skin capillary rarefaction in essential hypertension.

A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension. This rarefaction may play a role in increasing peripheral resistance. However, the mechanism underlying this capillary rarefaction is not understood. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of dorsum of fingers in essential hypertension. The capillary microcirculation was examined with video microscopy before and after maximizing the number of perfused capillaries by venous congestion. The study group comprised 17 patients with essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used intravital video microscopy with an epi-illuminated microscope to examine the skin of the dorsum of left middle phalanx before and after venous congestion at 60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at baseline in hypertensive subjects versus normotensive subjects. With venous occlusion, capillary density increased significantly in both groups; however, maximal capillary density remained significantly lower in the hypertensive subjects than in the normotensive subjects. The study strongly suggests that much of the reduction in capillary density in the hypertensive subjects is caused by structural (anatomic) absence of capillaries rather than functional nonperfusion.

Adult↗
PubMed1999

Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality.

We recently showed that rarefaction of skin capillaries in the dorsum of the fingers of patients with essential hypertension is due to the structural (anatomic) absence of capillaries rather than functional nonperfusion. It is not known whether this rarefaction is primary (ie, antedates the onset of hypertension) or secondary (ie, as a consequence of sustained and prolonged elevation of blood pressure [BP]). The aim of the present investigation was to study skin capillary density in a group of patients with mild borderline hypertension to assess whether rarefaction antedates the onset of sustained elevation of BP. The study group included 18 patients with mild borderline hypertension (mean supine BP, 136/83 mm Hg), 32 normotensive controls (mean BP, 126/77 mm Hg), and 45 patients with established essential hypertension (mean BP, 156/98 mm Hg). The skin of the dorsum of the fingers was examined by intravital capillary videomicroscopy before and after venous congestion at 60 mm Hg for 2 minutes. Patients with borderline essential hypertension had the lowest resting capillary density when compared with normotensive controls and patients with established hypertension. Maximal capillary density with venous congestion in the borderline group remained the lowest. The study confirmed that patients with borderline essential hypertension have skin capillary densities that are equally low as or even lower than patients with established hypertension. Both groups had significantly lower capillary densities than normal controls. One explanation for the results is that capillary rarefaction may be due to an early structural abnormality in essential hypertension.

Analysis of Variance↗
PubMed1999

Maximization of skin capillaries during intravital video-microscopy in essential hypertension: comparison between venous congestion, reactive hyperaemia and core heat load tests.

Intravital capillary video-microscopy is a dynamic method for studying skin capillaries. The technique of direct intravital microscopy (without dyes) depends on the presence of red blood cells inside capillaries for their identification. The aim of the present study was to compare different techniques to try to establish the best method for maximizing the number of visible perfused capillaries during intravital capillary microscopy. We compared the effects of venous congestion with those of post-occlusive reactive hyperaemia (Study 1). We also investigated venous congestion followed first by post-occlusive reactive hyperaemia and then by a core heat load test (Study 2). Finally we investigated venous congestion followed by post-occlusive reactive hyperaemia combined with venous congestion (Study 3). In Study 1, capillary density increased with venous congestion from a baseline value of 74+/-2 (mean+/-S.E.M.) per field to 82+/-3 per field (P<0.0001; analysis of variance). With reactive hyperaemia, there was an apparent decrease in visible capillary density to 69+/-2 per field. In Study 2, baseline capillary density was 69+/-4 per field, and this increased significantly with venous congestion to 74+/-4 per field (P=0.01). With both reactive hyperaemia and core heat load, the apparent density was 62+/-4 per field. In Study 3 the baseline density was 70+/-2 per field, and this increased significantly with venous congestion to 80+/-3 per field (P<0.0001). With reactive hyperaemia combined with venous congestion, the density was 81+/-3 per field (P=0.328 compared with venous congestion alone). The results show that venous congestion at 60 mmHg for 2 min is the most effective method for visualization of the maximal number of perfused skin capillaries during intravital video-microscopy.

Adult↗
PubMed1999

Nutrition and blood pressure.

Nutrition plays a very important role in regulating blood pressure. If we reverted to our evolutionary diet the problem of high blood pressure would disappear. However, this is unlikely and we, therefore, need to identify the most important factors in our diet that predispose to high blood pressure and, therefore, to vascular disease. Studies clearly demonstrate the very important role of our current intake of salt in our diet as being the major factor in regulating blood pressure in populations. Other dietary factors have also been identified as playing an important role, particularly potassium intake and fruit and vegetable consumption. A more healthy diet, that is a diet with much less salt and increased potassium through an increase in fruit and vegetable consumption, a reduction in fat intake with substitution of saturated by monounsaturated fat, a reduction in meat and dairy products with an increase in fish consumption will have large effects on blood pressure but, at the same time, will decrease other cardiovascular risk factors, particularly cholesterol and glucose intolerance. This healthier diet will reduce cardiovascular disease and is similar to the diet now being advocated for the prevention of some forms of cancer. Diet is by far the most important environmental factor determining our longevity and for those who wish to live longer, a change in diet as early in life as possible will have substantial effects.

Alcohol Drinking↗
PubMed1998

Association between atrial natriuretic peptide and cyclic GMP in hypertension and in chronic renal failure.

This study has examined the association between circulating atrial natriuretic peptide (ANP), plasma cyclic GMP and urinary cyclic GMP in relation to hypertension and reduced renal function in 30 normotensives, in 30 patients with essential hypertension and in 22 patients with stable dialysis-independent chronic renal failure (CRF). Plasma ANP was significantly raised (about two-three-fold) in the CRF group compared with the hypertensive and normal groups; plasma cyclic GMP was also significantly raised in the CRF group (median group values: 4.6, 5.8 and 11.0 pmol/ml, respectively, for the normal, hypertensive and CRF groups). There were no significant differences in urinary cyclic GMP between the normotensives and hypertensives but urinary cyclic GMP was significantly reduced in the patients with CRF (median group values: 407.1, 450.9 and 247.8 pmol/min for the normal, hypertensive and CRF groups, respectively, P < 0.001). In the subjects with CRF, the clearance of cyclic GMP was reduced in proportion to the clearance of creatinine, but there was no significant difference in the fractional excretion of cyclic GMP (median group values: 78.1% in the normal group, 78.9% in the hypertensive group and 70.2% in the CRF group). In all groups, there was no association between circulating ANP and urinary cyclic GMP: By contrast, there was a positive association between plasma ANP and plasma cyclic GMP (r = 0.39 P < 0.001) that was independent of blood pressure or renal function. These results demonstrate that while a substantial amount of urinary cyclic GMP originates from the glomerular filtrate, to some extent, raised plasma ANP also contributes to the circulating levels of cyclic GMP. However, plasma cyclic GMP cannot be taken as a direct substitute for plasma ANP.

Adult↗
PubMed1998

Association of hypertension with T594M mutation in beta subunit of epithelial sodium channels in black people resident in London.

BACKGROUND: Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation. METHODS: In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive (48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel beta subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing. FINDINGS: 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive participants possessed the T594M variant (odds ratio [OR]=4.17 [95% CI 1.12-18.25], p=0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR=5.52 [1.40-30.61], p=0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median=0.19 ng mL(-1) h(-1)) than in 39 untreated hypertensive individuals without the variant (median=0.45 ng mL(-1) h(-1), p=0.009). INTERPRETATION: Among black London people the T594M sodium-channel beta subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.

Black People↗
PubMed1998

Serotonin and heart rate in hypertensive and normotensive subjects.

Plasma and platelet levels of 5-hydroxytryptamine (5 HT) may be altered in essential hypertension. To establish the determinants and correlates of 5 HT in plasma and platelets, we studied 53 untreated subjects with essential hypertension (26 men; 30 whites; mean supine blood pressure 172/101 mm Hg; mean age 49.3 +/- 1.5 years) and 61 normotensive subjects (37 men; 47 whites; mean supine blood pressure 128/78 mm Hg; mean age 42.8 +/- 1.6 years). Plasma and platelet 5 HT were assayed by reverse-phase high performance liquid chromatography with electrochemical detection. No significant difference was found in platelet-poor plasma or platelet 5 HT levels in hypertensive or normotensive subjects (plasma: 43.0 +/- 4.2 and 39.6 +/- 4.4 nmol/L; platelet: 1.65 +/- 1.22 and 1.70 +/- 1.39 nmol/10(9) cells in hypertensive and normotensive subjects, respectively). No significant correlation was found between plasma or platelet 5 HT and systolic or diastolic blood pressure (plasma: r = 0.01 and 0.01 in normotensive subjects and r = 0.01 and -0.14 in hypertensive subjects; platelet: r = 0.12 and 0.13 in normotensive subjects and r = 0.02 and -0.09 in hypertensive subjects). However, plasma 5 HT was associated with supine and standing pulse rates (supine: r = 0.27, p = 0.05 in normotensive subjects and r = 0.54, p < 0.001 in hypertensive subjects; standing: r = 0.19 and r = 0.46, p < 0.001, respectively). Significant relations were also found between platelet 5 HT levels and supine and standing heart rate in the subjects mentioned above (supine: r = 0.28, p = 0.05 in normotensive subjects and r = 0.64, p < 0.001 in hypertensive subjects; standing: r = 0.24 and r = 0.51, p < 0.001, respectively). These associations were stronger in the hypertensive group as a whole, and they held when adjustment was made for differences in age and total blood cholesterol. The present study showed that plasma and platelet 5 HT are not significantly altered in hypertensive subjects. However, plasma and platelet 5 HT levels showed a significant association with supine and standing pulse rate predominantly in hypertensive subjects. This is consistent with experimental evidence of a positive chronotropic effect of 5 HT on perfused hearts and it suggests a possible role of plasma serotonin in the regulation of heart rate.

Adult↗
PubMed1998

How does treatment influence endocrine mechanisms in acute severe heart failure? Effects on cardiac natriuretic peptides, the renin system, neuropeptide Y and catecholamines.

1. Hormones involved in cardiovascular regulation are influenced by drug treatment. It is therefore difficult to study endocrine mechanisms in heart failure as most patients are already on treatment by the time they reach hospital. 2. We studied nine hospital in-patients before and after treatment of acute New York Heart Association class IV heart failure. 3. Before treatment, plasma brain and atrial natriuretic peptides were markedly elevated (BNP 121 +/- 26 pg/ml, ANP 163 +/- 33 pg/ml; normal range: BNP 3.9 +/- 0.3 pg/ml, ANP 8.6 +/- 0.8 pg/ml) and correlated positively with serum creatinine and left ventricular end-diastolic diameter and negatively with ejection fraction. Eight patients improved and one died. 4. With improvement plasma ANP and BNP fell. Initial renin activity was within the normal range but increased on treatment. Plasma neuropeptide Y and adrenaline remained normal before and after treatment in the eight patients who improved. Initial plasma noradrenaline was in the normal range in four of these patients and just above normal in a further four. In the patient who died, initial plasma neuropeptide Y and catecholamines were very high. 5. Plasma BNP emerged as complementary to ANP as a dynamic index in severe heart failure; however, renal function is also an important determinant of plasma BNP and ANP. There is little evidence for activation of the circulating renin-angiotensin-aldosterone system or neuropeptide Y before treatment of acute heart failure.

Acute Disease↗