Linford J. B. Briant

Sympathetic regulation of blood pressure in normotension and hypertension: when sex matters

What is the topic of this review? Hypertension is a major problem in Western society. Risk of hypertension increases with age, especially in women, who have lower risk compared with men until menopause. This review outlines the sex differences in the sympathetic control of blood pressure and how these mechanisms change with age. What advances does it highlight? It has recently been recognized that men and women regulate blood pressure by different physiological mechanisms. This is important for both the understanding and the clinical management of individual patients with hypertension. This review summarizes recent advances in understanding how the regulation of blood pressure in hypertension by the sympathetic nervous system differs between men and women.

Wellbeing, alcohol use and sexual activity in young teenagers: findings from a cross-sectional survey in school children in North West England.

BackgroundAdolescent health is a growing concern. High rates of binge drinking and teenage pregnancies, documented in the UK, are two measures defining poor wellbeing. Improving wellbeing through schools is a priority but information on the impact of wellbeing on alcohol use, and on sexual activity among schoolchildren is limited.MethodsA cross-sectional survey using self-completed questionnaires was conducted among 3,641 schoolchildren aged 11-14 years due to participate in a sex and relationships education pilot programme in 15 high schools in North West England. Bivariate and multivariate analyses were conducted to examine the relationship between wellbeing and alcohol use, and wellbeing and sexual activity.ResultsA third of 11 year olds, rising to two-thirds of 14 year olds, had drunk alcohol. Children with positive school wellbeing had lower odds of ever drinking alcohol, drinking often, engaging in any sexual activity, and of having sex. General wellbeing had a smaller effect. The strength of the association between alcohol use and the prevalence of sexual activity in 13-14 year olds, increased incrementally with the higher frequency of alcohol use. Children drinking once a week or more had 12-fold higher odds of any sexual activity, and 10-fold higher odds of having sex. Rare and occasional drinkers had a significantly higher odds compared with non-drinkers.ConclusionsThe relationship between wellbeing and alcohol use, and wellbeing and sexual activity reinforces the importance of initiatives that enhance positive wellbeing in schoolchildren. The association between alcohol use and sexual activity highlights the need for integrated public health programmes. Policies restricting alcohol use may help reduce sexual exposure among young teenagers.

Glucagon secretion from pancreatic α-cells.

Abstract Type 2 diabetes involves a ménage à trois of impaired glucose regulation of pancreatic hormone release: in addition to impaired glucose-induced insulin secretion, the release of the hyperglycaemic hormone glucagon becomes dysregulated; these last-mentioned defects exacerbate the metabolic consequences of hypoinsulinaemia and are compounded further by hypersecretion of somatostatin (which inhibits both insulin and glucagon secretion). Glucagon secretion has been proposed to be regulated by either intrinsic or paracrine mechanisms, but their relative significance and the conditions under which they operate are debated. Importantly, the paracrine and intrinsic modes of regulation are not mutually exclusive; they could operate in parallel to control glucagon secretion. Here we have applied mathematical modelling of α-cell electrical activity as a novel means of dissecting the processes that underlie metabolic regulation of glucagon secretion. Our analyses indicate that basal hypersecretion of somatostatin and/or increased activity of somatostatin receptors may explain the loss of adequate counter-regulation under hypoglycaemic conditions, as well as the physiologically inappropriate stimulation of glucagon secretion during hyperglycaemia seen in diabetic patients. We therefore advocate studying the interaction of the paracrine and intrinsic mechanisms; unifying these processes may give a more complete picture of the regulation of glucagon secretion from α-cells than studying the individual parts.

Sympathetic regulation of blood pressure in normotension and hypertension

What is the topic of this review? Hypertension is a major problem in Western society. Risk of hypertension increases with age, especially in women, who have lower risk compared with men until menopause. This review outlines the sex differences in the sympathetic control of blood pressure and how these mechanisms change with age. What advances does it highlight? It has recently been recognized that men and women regulate blood pressure by different physiological mechanisms. This is important for both the understanding and the clinical management of individual patients with hypertension. This review summarizes recent advances in understanding how the regulation of blood pressure in hypertension by the sympathetic nervous system differs between men and women.

δ‐cells and β‐cells are electrically coupled and regulate α‐cell activity via somatostatin

We used a mouse expressing a light‐sensitive ion channel in β‐cells to understand how α‐cell activity is regulated by β‐cells. Light activation of β‐cells triggered a suppression of α‐cell activity via gap junction‐dependent activation of δ‐cells. Mathematical modelling of human islets suggests that 23% of the inhibitory effect of glucose on glucagon secretion is mediated by β‐cells via gap junction‐dependent activation of δ‐cells/somatostatin secretion.

Quantifying sympathetic neuro-haemodynamic transduction at rest in humans: insights into sex, ageing and blood pressure control

We have developed a simple analytical method for quantifying the transduction of sympathetic activity into vascular tone. This method demonstrates that as women age, the transfer of sympathetic nerve activity into vascular tone is increased, so that for a given level of sympathetic activity there is more vasoconstriction. In men, this measure decreases with age. Test–re‐test analysis demonstrated that the new method is a reliable estimate of sympathetic transduction. We conclude that increased sympathetic vascular coupling contributes to the age‐related increase in blood pressure that occurs in women only. This measure is a reliable estimate of sympathetic transduction in populations with high sympathetic nerve activity. Thus, it will provide information regarding whether treatment targeting the sympathetic nervous system, which interrupts the transfer of sympathetic nerve activity into vascular tone, will be effective in reducing blood pressure in hypertensive patients. This may provide insight into which populations will respond to certain types of anti‐hypertensive medication.

Respiratory modulated sympathetic activity: a putative mechanism for developing vascular resistance?

Sympathetic activity exhibits respiratory modulation that is amplified in hypertensive rats. Respiratory modulated sympathetic activity produces greater changes in vascular resistance than tonic stimulation of the same stimulus magnitude in normotensive but not hypertensive rats. Mathematical modelling demonstrates that respiratory modulated sympathetic activity may fail to produce greater vascular resistance changes in hypertensive rats because the system is saturated as a consequence of a dysfunctional noradrenaline reuptake mechanism. Respiratory modulated sympathetic activity is an efficient mechanism to raise vascular resistance promptly, corroborating its involvement in the ontogenesis of hypertension.

Respiratory modulated sympathetic activity

Sympathetic activity exhibits respiratory modulation that is amplified in hypertensive rats. Respiratory modulated sympathetic activity produces greater changes in vascular resistance than tonic stimulation of the same stimulus magnitude in normotensive but not hypertensive rats. Mathematical modelling demonstrates that respiratory modulated sympathetic activity may fail to produce greater vascular resistance changes in hypertensive rats because the system is saturated as a consequence of a dysfunctional noradrenaline reuptake mechanism. Respiratory modulated sympathetic activity is an efficient mechanism to raise vascular resistance promptly, corroborating its involvement in the ontogenesis of hypertension.

Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration: a whole cell recording study in situ

Sympathetic preganglionic neurones (SPNs) gatekeep the activity flowing from the CNS to the periphery and their intrinsic properties are believed to play an important integrative role in determining the firing patterns. Previous cell recording studies have explored the electrophysiological characteristics of SPNs but until now it has not been possible to link this knowledge to their roles in cardiorespiratory integration. We used the working heart–brainstem preparation to make whole‐cell patch clamp recordings from thoracic SPNs (n = 98). The SPNs were classified into muscle vasoconstrictor‐like (MVClike, 39%) and cutaneous vasoconstrictor‐like (CVClike, 28%) on the basis of their dichotomous responses to cardiorespiratory reflex activation. The MVClike SPNs have higher baseline firing frequencies and distinctive intrinsic properties. Their firing is driven by a barrage of excitatory synaptic potentials with both tonic and respiratory modulated components. The CVClike SPNs show stereotyped rhythmical membrane potential oscillations that underpin their action potential discharge. We propose that these striking differences in the intrinsic properties of the classes of SPNs are likely to play an important role in patterning the sympathetic outflow.

Modelling the vascular response to sympathetic postganglionic nerve activity

This paper explores the influence of burst properties of the sympathetic nervous system on arterial contractility. Specifically, a mathematical model is constructed of the pathway from action potential generation in a sympathetic postganglionic neurone to contraction of an arterial smooth muscle cell. The differential equation model is a synthesis of models of the individual physiological processes, and is shown to be consistent with physiological data. The model is found to be unresponsive to tonic (regular) stimulation at typical frequencies recorded in sympathetic efferents. However, when stimulated at the same average frequency, but with repetitive respiratory-modulated burst patterns, it produces marked contractions. Moreover, the contractile force produced is found to be highly dependent on the number of spikes in each burst. In particular, when the model is driven by preganglionic spike trains recorded from wild-type and spontaneously hypertensive rats (which have increased spiking during each burst) the contractile force was found to be 10-fold greater in the hypertensive case. An explanation is provided in terms of the summative increased release of noradrenaline. Furthermore, the results suggest the marked effect that hypertensive spike trains had on smooth muscle cell tone can provide a significant contribution to the pathology of hypertension.