Control of mesenteric arterial tone in vitro in humans and rats

The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N ^G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K⁺ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca²⁺ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca²⁺-induced contractions in human arteries. Received: 1 October 1998 / Accepted: 4 January 1999     

Smoking behaviour and compensation: a review of the literature

Rationale: Compensation or compensatory smoking, accurately defined, deals with the question of whether switching to cigarette brands with different smoke yields is associated with a change in smoke uptake proportional to the change in machine-derived yields. The issue of compensation is important because it bears on whether switching to ”lighter” brands means lower overall smoke intake or not. Objectives: The present review investigated whether and to what extend low yield cigarettes are smoked more intensively. In addition, published data on whether nicotine, ”tar”, or any other smoke constituent or property influence compensational smoking are summarized. Methods: The studies on compensation were classified as follows: (1) studies on smoking behaviour in relation to cigarette yields (with and without brand switching); (2) studies on compensation for nicotine (switching between cigarettes which differ ”only” in their nicotine yield, nicotine supplementation, manipulation of renal nicotine excretion, administration of nicotine agonists or antagonists); (3) studies on compensation for other factors (influence of tar, taste, irritation, draw resistance). In order to quantify the degree of compensation, an index is defined and applied to selected brand switching studies. This compensation index determines, in relative units, the degree to which a smoker responds to a change in smoke yields with a change in smoke uptake measured by suitable biomarkers. The role of vent blocking is also briefly discussed. Results: Most of the studies which compare the smoking behaviour when smoking cigarettes with different smoke yields supply evidence for ”partial” compensation, suggesting that cigarettes with lower yields are smoked more intensively than those with higher yields. These studies also show that a change in the daily number of cigarettes is not a common mechanism of compensation. Effective vent blocking during smoking is a rare event and can therefore also be regarded as an uncommon mechanism of compensation. Evaluation of a suitable subset of brand-switching studies revealed an average compensation of 50–60% of the nicotine yield. Compensation tended to be more complete when changing to cigarettes with higher yields than when changing to cigarettes with lower yields. In general, brand-switching studies do not supply information on the underlying causal factors responsible for compensatory smoking. Results of the nicotine supplementation studies are not conclusive: some report evidence of nicotine titration, others do not. A general problem with this type of investigation is that continuous nicotine application does not mimic the spike-wise application with cigarette smoking, and may lead to nicotine tolerance. There is limited evidence that cigarettes were smoked more intensively when the urinary clearance of nicotine was increased. A small number of studies provide some evidence that smoking intensity increased after smokers were administered a nicotine antagonist. Several reports indicate that tar, taste and sensory properties of the smoke as well as the draw resistance of the cigarette may play a role in compensatory smoking. Low-yield cigarettes usually have reduced pressure drops which smoke researchers have suggested leads to increased puff volume. This effect seems to be independent of the smoke yield of the cigarette. There is also some evidence that some smokers maintain a consistent pattern of smoking which works independent of any changes in nicotine or tar yields, taste or design features of the cigarette (”functional autonomy”). Conclusions: The available data suggest that smokers partially compensate for a different smoke yield. While the factors and their interaction responsible for compensational smoking are not fully understood, there are data suggesting that a subgroup of smokers may partially compensate for nicotine. Even in this subgroup of smokers, however, the relative importance of the pharmacological versus the sensory effects of nicotine in smoke remains to be determined. Received: 4 January 1999 / Final version: 22 March 1999     

正常压力脑积水患者分流手术适应证的选择

探讨正常压力脑积水病人脑脊液分流手术适应证的选择。方法：选择经腰穿测压压力正常的脑积水患者,分析其临床特点和ＣＴ影像的特征性表现,及颅内压监测,手术结果。分流术效果：以痴呆发病者部分病人症状减轻或消失,。以步态障碍和尿失禁发病者症状基本得到控制。     

Fitness in the fit: does physical conditioning affect cardiovascular risk factors in middle-aged marathon runners?

OBJECTIVE: The study was designed to assess cardiovascular risk factorsin marathon runners with different degrees of fitness. DESIGN: A total of 30 male middle-aged marathon runners were dividedaccording to their marathon running time into fit (265 ±8 min), fitter (222 ± 5 min) and fittest (178 ±12 min). The three groups of 10 runners each were comparablein age, weight, and body surface area. Cardiovascular risk factorswere assessed by measuring arterial pressure before and duringexercise (150 watts) and determination of plasma lipoproteins,uric acid, glucose and white blood cell count before and aftera marathon run. RESULTS: All measured laboratory values such as high-density lipoproteincholesterol (P<0.05), low-density lipoprotein cholesterol(P <0.05), total cholesterol (non-significant), triglycerides(non-significant), blood sugar (non-significant), uric acid(P <0.05), and white blood cell count (P <0.05) indicateda lower cardiovascular risk in the fastest when compared withthe slowest runners. Resting blood pressure was similar in thethree groups but consistently lower at all levels of exercisein the fittest when compared with the less fit runners. Thefittest runners also showed greater increases in high-densitylipoprotein cholesterol after the marathon run (14% vs 8% inthe slowest runners, P<0.05). CONCLUSIONS: We conclude that even at the extreme end of a continuum suchas represented by well-conditioned, middle-aged marathon runners,cardiovascular risk factors are related to the degree of fitness,as measured by the marathon running time.     

Long-term lowering of blood pressure after carotid and vertebrobasilar ischemic stroke

We followed up 107 patients experiencing a first-ever ischemic stroke after having been affected by essential hypertension for at least one year, in order to analyze the phenomenon of post-stroke blood pressure lowering. Of the 82 patients still surviving after three months of follow-up, 44 (54%) had normal arterial blood pressure values. There were no significant differences between these normotensive patients and the 38 with high blood pressure in terms of cerebrovascular risk factors or disability, but blood pressure normalized in 34 of the 54 patients experiencing a carotid stroke (63%) and in only 10 of the 28 experiencing vertebrobasilar stroke (36%) (p=0.035). These data may offer a starting point for further studies of the neurogenesis of arterial hypertension.

---

Sommario Al fine di analizzare il fenomeno della normalizzazione della pressione arteriosa dopo ictus cerebrale in pazienti prima ipertesi, abbiamo osservato 107 soggetti con primo ictus ischemico, che erano già precedentemente affetti da ipertensione arteriosa da almeno un anno. Degli 82 (77%) sopravvissuti a tre mesi di follow-up, 44 (54%) hanno mostrato una normalizzazione della pressione arteriosa. L'incidenza di fattori di rischio per malattia cerebrovascolare e disabilità grave non è risultata significativamente diversa nel gruppo degli ipertesi rispetto ai normotesi. Tuttavia la normalizzazione della pressione arteriosa è stata osservata in 34 dei 54 pazienti con ictus carotideo (63%) e solo in 10 dei 28 con ictus vertebrobasilare (36%) (p=0.035). Riteniamo che tali dati offrano uno spunto per ulteriori ricerche sulla genesi neurogena dell'ipertensione arteriosa essenziale.

     

Relationship between anterior fontanelle pressure measurements and clinical signs in infantile hydrocephalus

The treatment of choice in progressive hydrocephalus is drainage of cerebrospinal fluid in order to reduce elevated intracranial pressure (ICP). Defining the right moment for surgical intervention, however, in a hydrocephalic infant on the basis of clinical signs alone can be a difficult task. Clinical signs of raised ICP are known to be unreliable and sometimes even misleading. In the present study, the relationship between long-term anterior fontanelle pressure (AFP) measurements and clinical signs was investigated in 37 infants with hydrocephalus. The decision as to whether to operate or not was based on clinical signs alone; AFP values were not taken into account. There was an overall difference between the non-operated group and the preoperative measurements in the operated group, and also between the preoperative and the postoperative measurements in the latter, in regard to both AFP measurements and clinical signs. Almost all preoperative AFP values were increased. The direct correlation () between most individual clinical signs and AFP levels, however, was low (=0.15–0.41). The clinical sign tense fontanelle showed the best correlation with the AFP levels (=0.75). Furthermore, using logistic regression analysis, no combination of clinical signs could be found which reliably predicted the AFP. The relationship between the AFP pressure variables and clinical signs was also examined. The pathological A-waves occurred only in the presence of raised (baseline) AFP, a situation in which considerably more frequent B-waves were observed as well. It was concluded that clinical signs of raised ICP in infantile hydrocephalus are not very reliable and AFP monitoring can therefore provide valuable information on intracranial dynamics in patients with dubious neurological manifestations of progressive hydrocephalus.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: ROLE OF AT1 RECEPTORS IN THE CENTRAL CONTROL OF SYMPATHETIC VASOMOTOR FUNCTION

• 1 In a number of species, high concentrations of angiotensin II (AngII) receptors have been found in the rostral ventrolateral medulla (RVLM) in the hindbrain, which is an important region involved in the modulation of sympathetic vasomotor tone. The present review describes studies in which the contribution of angiotensin receptors in the brainstem to cardiovascular regulation, in particular sympathetic vasomotor reflexes, has been examined in conscious and anaesthetized rabbits.
• 2 In conscious rabbits, fourth ventricular infusions of AngII produced dose-dependent pressor responses as doses 400 times less than equipressor intravenous doses. Chronic baroreceptor denervation increased the sensitivity to AngII by 1000-fold. Administration of prazosin i.v. blocked the pressor response, suggesting that the mechanism involved sympathetic vasoconstriction.
• 3 The pattern of haemodynamic changes in response to AngII injected into the fourth ventricle (4V) involved decreased total peripheral conductance and mesenteric conductance, but a rise in hindlimb conductance. Sinoaortic denervation changed the hindlimb fall in conductance to an increase, suggesting that muscle vasomotor pathways were particularly inhibited by baroreceptor feedback mechanisms.
• 4 In anaesthetized rabbits, infusion of AngII into the RVLM increased blood pressure and transiently increased resting renal sympathetic nerve activity. The renal sympathetic baroreflex curves were shifted to the right and the upper plateau of the sympathetic reflex increase was markedly increased.
• 5 The pressor actions of 4V AngII were blocked by administration of a peptide antagonist injected into the RVLM or by the angiotensin AT₁ antagonist losartan injected into the 4V. These results suggest that mainly AT₁ receptors are involved and that the RVLM is a likely candidate site for the modulation of the renal sympathetic baroreflex.
• 6 Losartan administration into the 4V in conscious rabbits increased resting renal sympathetic tone and enhanced renal sympathetic baroreflex and chemoreflexes.
• 7 Our studies suggest that there are sympathoexcitatory AT₁ receptors in the RVLM accessible to AngII from the cerebrospinal fluid. In addition, an AT₁ receptor pathway normally inhibits the sympathoexcitation produced by baroreceptor unloading or chemoreceptor activation. The effect of losartan suggests that there is greater tonic activity within the sympathoinhibitory pathways. These two actions suggest that angiotensin receptors in the brainstem modulate sympathetic responses to specific afferent inputs, thus forming part of a potentially important mechanism for the integration of characteristic autonomic response patterns.

     

The acute cardiovascular actions of intravenous thyrotrophin releasing hormone (TRH) in man are mediated by non-catecholaminergic mechanisms

1. Intravenous bolus doses of thyrotrophin releasing hormone (TRH, 50–1000 μg) caused statistically significant, non-dose dependent and transient rises in blood pressure, heart rate and plasma catecholamines in healthy young males.
2. Mean peak incremental rises in systolic blood pressure (mean ± s.e. mean) following 50, 200 and 500 μg TRH were 14.3 ± 2.9 mmHg, 15.7 ± 3.2 mmHg and 17.1 ± 3.9 mmHg respectively (all P < 0.05 vs placebo). Mean incremental rises in heart rate for the three doses of TRH were 8.2 ± 2.2 beats min⁻¹, 7.1 ± 1.8 beats min⁻¹, and 1O.7 ± 2.9 beats min⁻¹ respectively (all P < 0.05 vs placebo).
3. Following the 50 μg and 1000 μg doses of TRH, plasma noradrenaline and adrenaline rose significantly (P < 0.05) between 4 and 8 min. Mean ± s.e. mean incremental plasma noradrenaline rise following 50, 200 and 1000 μg TRH were 0.4 ± O.13 nmol 1⁻¹, 0.37 ± 0.21 nmol 1⁻¹ and 0.41 ± 0.18 nmol 1⁻¹ respectively. Mean ± s.e. mean incremental rise in adrenaline for the 50, 200 and 1000 μg dose were 0.13 ± 0.04 nmol 1⁻¹, 0.08 ± 0.03 nmol 1⁻¹, and 0.11 ± 0.05 nmol l⁻¹ respectively.
4. Following administration of the ganglion blocking drug pentolinium (5 mg) the incremental systolic blood pressure and heart rate rises following 500 μg TRH alone 16.6 ± 2.8 mmHg and 1O.4 ± 3.1 beats min⁻¹ respectively.
5. The rises in plasma noradrenaline and adrenaline following TRH were attenuated by prior ganglion blockade.
6. α-adrenoceptor blockade with thymoxamine (0.3 mg kg⁻¹ bolus + 0.3 mg kg⁻¹ h⁻¹ infusion), singly and combined with intravenous propranolol (10 mg i.v. over 10 min), did not alter the pressor or tachycardic effects of 500 μg TRH.
7. In conclusion, although plasma noradrenaline rises following i.v. TRH, suggesting activation of the sympathetic nervous system, this effect is not responsible for the pressor response to TRH, which appears to be due to either a direct vasoconstrictive effect on the peripheral resistance vessels or a direct inotropic/chronotropic effect on the heart.

     

CO2 and indomethacin vasoreactivity in patients with head injury

Summary The purpose of this study was to compare the effect of hyper-ventilation and indomethacin on cerebral circulation, metabolism and pressures in patients with acute severe head injury in order to see if indomethacin may act supplementary to hyperventilation. Fourteen severely head injured patients entered the study. Intracranial pressure (ICP), mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored continuously. Within the first four days after the trauma the CO₂ and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous¹³³Xe technique) and arterio-venous difference of oxygen (AVdO₂). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO₂), lactate and lactate/oxygen index (LOI). Data are presented as medians and ranges, results are significant unless otherwise indicated. Before intervention ICP was well controlled (14.8 (9–24) mmHg) and basic CBF level was 39.1 (21.6–75.0) ml/100 g/min). The arterio-venous oxygen differences were generally decreased (AVdO₂ = 4.3 (1.8–8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO₂ were decreased (1.54 (0.7–3.2) ml/100 g/min) as well.Duringhyperventilation (APaCO₂ = 0.88 (0.62–1.55) kPa) CBF decreased with 11.8 (–33.4–29.7) %/kPa and ICP decreased with 3.8 (0–10) mmHg. AVdO₂ increased 34.0 (4.0–139.2) %/kPa, MABP was unchanged, CMRO₂ and CPP increased (CPP = 3.9 (–10–20) mmHg). AVD (lactate) and LOI were unchanged. No correlations between CBF responses to hypocapnia and outcomes were observed.An i.v. bolus dose ofindomethacin (30 mg) decreased CBF 14.7 (–16.7–57.4) % and ICP decreased 4.3 (–1–17) mmHg. AVdO₂ increased 27.8 (–40.0–66.7)%, MABP (MABP = 4.9 (–2–21) mmHg) and CPP (CPP = 8.7 (3–29) mmHg) increased while CMRO₂ was unchanged. No changes in AVd (lactate) and LOI indicating cerebral ischaemia were found.Compared to hyperventilation (changes per 1 kPa, at PaCO₂ level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO₂, ICP, SvjO₂, and LOI were of the same order of magnitude.Nocorrelation between relative reactivities to indomethacin and CO₂, evaluated from changes in CBF and AVdO₂, or between the decrease in ICP after the two procedures were found. Thus, some patients reacted to indomethacin but not to hyperventilation, and vice versa.These results suggest that indomethacin and hyperventilation might act independently, or in a complementary fashion in the treatment of patients with severe head injury.     

Prevalence survey of movement disorders, epilepsy, hypertension and smoking habit in Vejer de la Frontera, Southern Spain-I. Methodology

A prevalence survey of movement disorders, epilepsy, hypertension and smoking was undertaken in Vejer de la Frontera, Southern Spain in 1988. A validated screening instrument designed for door-to-door tracing of specific disorders was used. Neurological diagnoses were based on: (1) direct anamnesis and examination by a senior neurologist; (2) perusal of existing medical records; and (3) in a proportion of cases, a hospital-based complementary study. This experience suggests that, while door-to-door surveys of neurological disorders have focused on multiple major outcomes: (1) scientific and logistic reasons can exist for screening for specific neurological disorders, and (2) scientific and public health-related interventional objectives can be combined advantageously when such costly investigations are conducted.