Peter C. Rubin

Noradrenaline release and clearance in relation to age and blood pressure in man

Abstract. Plasma noradrenaline concentration increases with age. This study was designed to investigate whether an increased rate of noradrenaline release into the circulation or a decrease in clearance is primarily responsible for this age related change in concentration. Sixteen healthy male subjects were studied, eight young (21–36 years) and eight old (65–78 years). Clearance was calculated from steady state noradrenaline concentrations during constant rate infusions of unlabelled noradrenaline. Clearance did not differ between the two groups: young 4.8 1/min (range 2.7–6.1), old 4.1 (range 2.6–8.2). The old subjects had significantly greater rates of release. Supine: young 10.3 nmol/min (range 5.3–17.6), old 19.7 (range 10.1–30), P<0.05. Standing: young 17.2 (range 11–36.4), old 29.2 (range 21.8–47.9), P<0.01. No significant relationship was found in either supine or standing position between rate of noradrenaline release and either systolic or diastolic blood pressure. These results indicate that plasma noradrenaline concentration rises with age because of an increased rate of release, but that this increased release is not responsible for the higher blood pressure seen in the elderly.

Obstetric aspects of the use in pregnancy-associated hypertension of the β-adrenoceptor antagonist atenolol+

The obstetric implications of the use of the beta-adrenoceptor antagonist atenolol have been evaluated in a prospective, randomized, double-blind, and placebo-controlled study involving 120 women with pregnancy-associated hypertension. The clinical interpretation of antenatal and intrapartum cardiotocographs was uninfluenced by atenolol. Human placental lactogen concentration fell in the atenolol group, but this was not an indicator of subsequent fetal distress. Other obstetric indices, such as urinary estriol excretion, were the same in both groups. Spontaneous premature labor occurred in five women receiving placebo but in none who received atenolol. Together with previously reported findings on pregnancy outcome, our study leads us to conclude that beta-blockers such as atenolol can appropriately be used in the management of hypertension during pregnancy.

Opioid Peptides and Central Control of Blood Pressure

The role of endogenous opioids in central modulation of baroreceptor reflex function has been assessed in rabbits and in man using stable enkephalin analogues and synthetic opiates with a range of mu, delta and kappa opiate receptor agonist specificity. In addition the effects of naloxone, a mu opiate receptor antagonist, have been studied. In rabbits descarboxy-leu-enkephalin (RX783016) given by intracisternal injection reduced baroreflex sensitivity as assessed by heart rate responses to phenylephrine, sodium nitroprusside and controlled haemorrhage. These effects were prevented by intravenous naloxone. Naloxone alone increased the slope of the heart period: mean arterial pressure relationship and thus increased baroreflex sensitivity. In conscious man essentially similar results were found following intravenous dosing with a stable met-enkephalin analogue (DAMME, FK33824) or naloxone with decreases and increases respectively in the sensitivity of baroreflex responses to sodium nitroprusside. In rabbits and man arterial baroreceptor reflexes mediating heart rate responses can be pharmacologically modified by exogenous opiates and may be under some tonic endogenous opiate peptide influences.

Reappearance of end-diastolic velocity in a pregnancy complicated by severe pregnancy-induced hypertension

A case is reported in which previously absent end-diastolic velocities in the umbilical artery reappeared after treatment in a pregnancy complicated by hypertension. This observation is not consistent with the suggestion that abnormal waveforms are associated with obliteration of the tertiary stem villus arterioles.

Daily variability of umbilical and lateral uterine wall artery blood velocity waveform measurements.

Summary. The daily variability of umbilical artery and lateral uterine wall artery velocity‐time waveforms recorded by continuous wave Doppler ultrasound was determined by making three observations in each of 97 women on different days within a 7‐day period. There were no significant changes in the maximal:minimal Doppler shift frequency (A/B ratio) or the pulsatility index in either artery over the period of study. Common pregnancy complications did not influence the variability of the recordings. The variability of uterine artery recordings was not affected by gestational age between 17 and 41 weeks but the degree of variability of the umbilical artery recordings was greater before 30 weeks. We conclude that after 30 weeks gestation this technique has an acceptable range of daily variability for clinical and research applications.

Pharmacodynamic studies with a specific alpha 2-adrenoceptor agonist (BHT-933) in man.

We conducted pharmacodynamic studies in man with a specific alpha 2-adrenoceptor agonist BHT-933. The study involved nine male normotensive volunteers each of whom received BHT-933 5 mg or placebo in random order. BHT-933 significantly lowered systolic and diastolic blood pressure (BP) in supine and standing positions, the greatest effect occurring 3-4 h following drug administration. Supine values: placebo 116/73; BHT-933 99/64. Standing values: placebo 114/79; BHT-933 92/67. Heart rate was uninfluenced by BHT-933 even at the time of maximum fall in BP. Plasma noradrenaline concentration in the supine position was significantly reduced: placebo 2.5 +/- 0.8 nmol/L; BHT-933 1.7 +/- 0.6. The haemodynamic changes accompanying Valsalvas manoeuvre and cold pressor test were uninfluenced by BHT-933. All subjects experienced sedation and dry mouth following BHT-933 with a time course similar to that of the fall in BP. These results are consistent with an effect of BHT-933 on BP control through an action on alpha 2-receptors at the level of the brainstem.

Beta-Blockers in Pregnancy

DRUGS that competitively antagonize the effects of catecholamines at beta-adrenoreceptors have been in clinical use since the mid-1960s. Although they were initially used for the prevention of angi...

Umbilical artery blood velocity waveform analysis in predicting the small-for-dates fetus

Doppler umbilical artery blood velocity waveforms were recorded longitudinally in 78 randomly selected pregnancies. The waveform maximal (A) to minimal (B) Doppler shift frequency ratios were determined to provide a semi-quantitative measure of impedance to blood flow in the fetoplacental circulation. Fifty-eight of these pregnancies and their outcomes were normal. The A/B ratios from this normal group were used to derive a normal range of this index throughout the second half of pregnancy. A further 45 pregnancies, also randomly selected, were studied once within 2 weeks of delivery. Using those measurements, plus those from the longitudinal groups sampled within 2 weeks of delivery, the predictive values of the A/B ratio in detecting the small for gestational age fetus have been derived. The sensitivity of the umbilical artery A/B ratio in predicting a small for gestational age infant within 2 weeks of delivery was 58% with a specificity of 94%. The positive test predictive value was 69% with a negative test predictive value of 90%. These predictive values are lower than those previously published, probably because high-risk pregnancies were over-represented in earlier studies. Waveform analysis within 2 weeks of delivery did, however, appear to identify fetuses destined to develop a range of perinatal problems. Large prospective studies are needed before the predictive value of Doppler waveform analysis is clarified.