Aortic and inferior vena caval balloons were used to alter mean arterial blood pressure, pulse pressure ( PP ), and right atrial pressure ( RAP ) in unanesthetized rabbits and to reflexly evoke changes in heart period (pulse interval). Curves relating mean arterial blood pressure to heart period were compared in different groups of rabbits at similar Δ PP and Δ RAP . Median blood pressure ( BP 50 ), average gain (G), and heart period range (maximum to minimum heart period) were calculated from the S-shaped curves. The reflex was evoked from arterial baroreceptors and probably from cardiac and pulmonary baroreceptors. Curves relating mean arterial blood pressure and heart period differed with regard to BP 50 and G in sham-operated, thalamic, and pontine rabbits, indicating that suprabulbar centers normally play a role in the reflex. Curves from sham-operated and pontine rabbits treated with atropine also differed, suggesting suprabulbar control of sympathetic effectors. In intact rabbits, forebrain and diencephalic centers caused vagal and sympathetic effectors to respond over the same arterial blood pressure range, but, in pontine rabbits, the effectors responded over dissimilar ranges. In intact rabbits, changes in mean arterial blood pressure evoked reciprocal and nearly equal changes in vagal and sympathetic effectors, but, in pontine rabbits, a given pressure change altered heart period predominantly through one effector. In sham-operated rabbits, vagal effects on heart period were lower by a constant amount at every level of mean arterial blood pressure than they were in pontine rabbits, suggesting that suprabulbar centers exerted a tonic inhibitory effect on vagal motoneurons not involved in the reflex.

Iliac bed vascular resistance (IVR) was measured before and after pharmacological block of the autonomic effectors in unanaesthetized renal hypertensive and normotensive rabbits with previously implanted Doppler flowmeters. This permitted partitioning the resting IVR into a non-autonomic component (ie, steady-state IVR after block) and an autonomic component (ie, resting IVR minus non-autonomic IVR). When IVR was measured at the same mean arterial pressure (MAP) before and after block in each animal, the increase in estimated non-autonomic IVR accounted entirely for the rise in resting IVR in renal hypertensive rabbits. However, if IVR measurements after block were made at a lower MAP than before block, the estimated non-autonomic and autonomic components were both significantly increased in renal hypertensive rabbits. It is concluded that in the latter experiment non-autonomic IVR in renal hypertension was underestimated, whilst the autonomic component was overestimated. The rise in non-autonomic IVR in renal hypertension was partly due to structural changes in the iliac bed, since IVR remained higher in hypertensive than in normotensive rabbits after abolishing smooth muscle tone with vasodilator drugs.

The circulatory effects of blocking cardiac and peripheral autonomic effectors were studied in 32 subjects with established essential hypertension, and in 15 normotensives. The mean resting arterial pressure, heart rate and total peripheral resistance index (TPRI) were significantly higher in the hypertensives, but cardiac index was the same in both groups. In subjects with blocked cardiac effectors (atropine + beta-blocking drugs, i.v.) the sympathetic constrictor effects on TPRI were estimated from the changes after giving i.v. guanethidine + phentolamine. The autonomic component of TPRI was higher in hypertensives than in normotensives. The residual resistance after `total' autonomic block (non-autonomic TPRI) was higher in hypertensives, accounting for 60 to 80% of the initial difference in resting TPRI between the two groups. With an increase in non-autonomic TPRI, the increased autonomic TPRI effect in hypertension is not necessarily due to increased sympathetic nerve activity. Vagal and cardiac sympathetic effects on heart rate were compared in the two groups. Each estimate was based on the average of the responses to the appropriate blocking drug (1) in subjects not previously given a blocking drug, and (2) in subjects with the other cardiac effector pathway already blocked. The higher heart rate in established hypertension was predominantly due to change in vagal rather than cardiac sympathetic effects.

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SUMMARY We have assessed resting myocardial contractility and its baroreflex control in normotensive and hypertensive conscious rabbits. Hypertension was induced by bilateral cellophane wrapping of the kidneys with experiments performed 6 weeks later during the established phase of hypertension. The peak rate of change of left ventricular pressure (peak LV dP/dt) was used as the index of myocardial contractility. Baroreflex control of contractility and heart period (HP) was assessed by constructing stimulus response curves relating change in mean arterial pressure (MAP), induced by balloon occluders around the abdominal aorta and inferior vena cava, to change in peak LV dP/dt and HP. These stimulus response curves were obtained in normotensive rabbits with and without cardiac pacing, and in both normotensive and hypertensive animals after cardiac beta sympathetic blockade with propranolol, vagal blockade with methylscopolamine, and combined cardiac autonomic blockade with propranolol and scopolamine, as well as in rabbits with intact autonomic effectors.Resting MAP was significantly higher in the hypertensive rabbits (119 ± 2 mm Hg) compared to normotensive controls (76 ± 1 mm Hg). Resting peak LV dP/dt was also greater by 51% in the hypertensive animals (7054 ± 287 mm Hg sec" 1 ) compared to controls (4690 ± 223 mm Hg sec" 1 ). There was no significant difference in the resting heart period or resting left ventricular end diastolic pressure. Transient changes in MAP induced by occlusion of the aortic or venous balloons produced significant alterations in peak LV dP/dt in normotensive animals with and without pacing and in hypertensive control animals. In animals with cardiac sympathetic block, the range and slope or sensitivity of the stimulus response curves were not significantly changed but in animals with vagal blockade the sensitivity was reduced by 90% and the range at 30 mm Hg by 88%. After propranolol and methylscopolamine were administered together, the stimulus no longer evoked a response. These experiments demonstrate that myocardial contractility is under baroreflex control and suggest that this is mediated principally via parasympathetic nerves to the heart. There was no significant difference between the sensitivity of baroreflex control of myocardial contractility in the normotensive ( -8 4 ± 14 mm Hg sec" 1 per mm Hg) and the hypertensive (-110 ± 14 mm Hgsec" 1 per mm Hg) rabbits, unlike the baroreflex control of heart period where sensitivity was markedly impaired in the hypertensive (sensitivity 3.8 ± 0.8 msec/mm Hg) compared to the normotensive (6.9 ± 1 . 0 msec/mm Hg) animals. (Hypertension 5: 916-926, 1983) KEY WORDS • left ventricular pressure * mean arterial pressure • cardiac pacing • balloon occlusion • parasympathetic nerves M YOCARDIAL contractility has not been extensively studied in hypertension. Indeed there are no studies of myocardial contractility in the early stages of clinical human hypertension, and such evidence as there is in relation to experimental hypertension is conf...

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phages was still five times greater than control numbers and this could have been related to lack of complete recovery in permeability, which we found in our subjects after stopping smoking. We have not found a relation between amount smoked and the change in number of alveolar macrophages, and it would be interesting to compare the result of such a study with our finding of a relation between carboxyhaemoglobin and half-time clearance.The large change in the results of the permeability test and lack of effect on tests of ventilatory function are noteworthy. This implies that the alveolar permeability to the tracer 99mTc-DTPA is a very sensitive test of pulmonary dysfunction in cigarette smokers and the results are correlated with exposure to tobacco smoke. During the 21 days after stopping smoking recovery into the normal non-smoking range was the exception, and the greatest degree of recovery occurred in those with least exposure to tobacco smoke. Cation transport across the red-cell membrane was studied in subjects with essential hypertension and their relatives using rubidium-86 as an analogue of potassium. The activity of the ouabain-sensitive sodium-potassium pump was significantly greater in patients with untreated essential hypertension than in controls (p <0 001). No clear separation was seen between normotensive and hypertensive subjects. Activity of the sodium-potassium pump was also increased in a proportion of normotensive relatives of subjects with essential hypertension. Rubidium uptake was significantly lower in normotensive black subjects than in normotensive whites, the difference being in a ouabain-resistant pathway of cation transport. These results provide further evidence that a defect in membrane cation transport contributes to the pathogenesis of essential hypertension.

I Plasma concentrations of oxprenolol have been compared in six healthy volunteers after 80 and 160 mg doses of a new slow release (SR) oxprenolol preparation, after an 80 mg dose of conventional oxprenolol (CO), and after the second of two 80 mg doses of conventional oxprenolol given 12 h apart. Basal pulse rates and blood pressures, and pulse rates before and after a standard exercise test have been compared after the four active treatments and after a placebo. 2 Peak plasma concentrations of oxprenolol attained after 160 mg of the slow release preparation were similar to the peak concentrations after the single 80 mg dose of conventional oxprenolol. Higher concentrations, however, persisted for much longer after the slow release preparations than after the conventional preparations. 3 Neither oxprenolol formulation had any effect on resting pulse rate or blood pressure in normotensive volunteers. 4 Comparison with placebo showed that the single dose of the conventional oxprenolol produced a significant reduction in exercise induced tachycardia for 8 h whereas the high dose of the slow release preparation produced a similar reduction which lasted for at least 14 hours.