John V. Jones

Neural and Humoral Mechanisms Involved in Blood Pressure Variability

In order to study blood pressure variability we have measured blood pressure, heart rate, plasma noradrenaline and adrenaline concentration and plasma renin activity during sleep and during the waking process in 20 subjects with borderline hypertension. The responses to a number of standardized tests were also measured. These were reading, mental arithmetic, change in posture, physical exercise and the response to intravenously injected phenylephrine and noradrenaline. The sensitivity of the baroreflex for heart rate control was also determined from the relationship between heart period (R-R interval) and change in systolic pressure after the injection of phenylephrine. Blood pressure was also recorded continuously for 24 hours. From the lowest levels achieved during sleep, blood pressure rose as the subjects regained consciousness but was not restored to its baseline value until mental activity was also restored by reading. Blood pressure rose further with mental arithmetic. These changes were accompanied by a greater proportional rise in plasma adrenaline than in plasma noradrenaline concentrations. Plasma renin activity changed little. The pressor responses to phenylephrine and noradrenaline were inversely related to baroreceptor sensitivity. The fall in blood pressure with sleep and the rise with mental arithmetic was also inversely related to the sensitivity of the reflex. Systolic pressure recorded throughout the day was inversely related to the R-R interval in each subject. The slope of this relationship and range of R-R interval was greatest in the subjects with the most sensitive baroreflexes.

Consequences of impaired arterial baroreflexes in essential hypertension: effects on pressor responses, plasma noradrenaline and blood pressure variability

In 62 untreated patients with essential hypertension, arterial baroreflex sensitivity (BRS) for heart rate, i.e. the change in pulse interval in response to a phenylephrine-induced increase in blood pressure, was compared with (1) haemodynamic changes during mental arithmetic, a reaction time test, isometric and bicycle exercise; (2) plasma noradrenaline (PNA) concentrations at rest, and during bicycle exercise and; (3) the variability of ambulatory intra-arterial blood pressure. Subjects with diminished BRS showed the following responses: (1) higher mean arterial blood pressure (MAP) during all four stimuli; (2) a greater pressor response to cycling; (3) tended to have higher PNA concentrations during bicycle exercise and; (4) greater variation in ambulatory blood pressure. Furthermore, an increased pressor response to the reaction time test and increased ambulatory blood pressure variability was seen in younger subjects with reduced BRS. When subjects were subgrouped according to their WHO stage of hypertension, there were significant inverse relationships between BRS and the pressor responses to mental arithmetic, the reaction time test and cycling, and with ambulatory blood pressure variability only in those subjects without ECG or radiographic evidence of left ventricular enlargement (WHO stage I hypertension; n = 42). None of these correlations were present in subjects with one or both of these clinical findings (WHO stage II; n = 20). Pressor responses to the four laboratory stimuli and ambulatory blood pressure variability were similar in both groups, despite significantly higher arterial pressure and significantly lower BRS in WHO stage II subjects. These results suggest that differing mechanisms may be responsible for the regulation of blood pressure variation in these two groups. The arterial baroreflex can buffer acute changes in blood pressure in subjects with WHO stage I hypertension, but this ability is attenuated with progressive reduction of BRS. With the development of clinically evident cardiac adaptation to hypertension (WHO stage II), the contribution of the arterial baroreflex to the regulation of blood pressure is no longer detectable and the influence of cardiac and somatic afferents to reflex circulatory adjustments to activity may predominate.

Pressor responses to laboratory stresses and daytime blood pressure variability.

We studied 56 patients with essential hypertension to determine whether responses to standardized laboratory mental and physical challenges accurately reflect blood pressure variability during routine daily activities. Four activities were performed in the laboratory: mental arithmetic, a reaction time test, isometric exercise, and submaximal bicycle exercise. Blood pressure was measured directly from a brachial artery catheter. We then recorded intra-arterial ambulatory blood pressure away from hospital over 24 h. A frequency histogram was constructed from all cardiac cycles when subjects were awake. Variability of ambulatory blood pressure was defined as the standard deviation about the mean waking value. The increase in mean arterial pressure (MAP) during each of these four challenges correlated significantly with the variability of mean arterial pressure (highest correlation: reaction time test, r = 0.53, P less than 0.00001; lowest correlation: mental arithmetic, r = 0.26, P less than 0.03), and five subjects who were highly reactive to all four challenges also demonstrated increased blood pressure variability. We therefore conclude that these commonly used laboratory tests can give some information about the behaviour of blood pressure in daily life in some subjects, but overall the variance in blood pressure variability that can be accounted for by the pressor response to these standardized challenges is low.

Demonstration of choline acetyltransferase activity in the carotid body of the cat

1. The distribution of choline acetyltransferase in the carotid body of the cat has been investigated with the electron microscope to determine sites of enzymic activity. This is of relevance to the possible role of acetylcholine as a transmitter in the carotid body.

The fine structural localization of cholinesterases in the carotid body of the cat

1. The distribution of cholinesterases in the carotid body of the cat has been investigated with the electron microscope to obtain a clearer picture of the localization of the enzyme. This is of relevance to the possible role of acetylcholine as a transmitter in the carotid body.

Adverse effect of chronic alcohol ingestion on cardiac performance in spontaneously hypertensive rats

We have compared the cardiac performance of four groups of rats: normotensive control rats (NCR) and spontaneously hypertensive rats (SHR) not drinking alcohol, and NCR and SHR drinking 20% alcohol (NCR-A and SHR-A, respectively), over a period of 6-9 months.

Cholinesterase histochemistry of the rabbit distal colon

SummaryThe distribution of cholinesterase in the rabbit distal colon has been studied using histochemical methods. Non-specific cholinesterase predominates in muscle tissue, the longitudinal layer of the muscularis externa staining slightly more strongly than the circular layer. The muscularis mucosae stains the most intensely but its non-specific cholinesterase is markedly inactivated by 20 hr fixation in formaldehyde. Specific cholinesterase is present in ganglion cells in the myenteric and submucous plexuses, and these cells vary in staining intensity. Nerve fibres which stain for specific cholinesterase are present in the nerve plexuses and in the muscle layers. It is concluded that there are cholinergic nervous elements in the myenteric and submucous plexuses and in the muscle layers of the rabbit distal colon.

Editorial: Hypertension and the cerebral circulation.

Hypertension, and particularly its management, is frequently associated with cerebral dysfunction. In hypertensive encephalopathy the neurological manifestations are related to the very high blood pressure. Conversely, when a patient is treated intensively with antihypertensive drugs, cerebral dysfunction may result from the reduction in blood pressure. In either situation, clinical symptoms have long been thought to be associated with changes in blood flow to the brain. Despite this detailed studies have only recently been made of the cerebral circulation during changes in blood pressure. Since 1948 it has been known that in hypertensive patients the absolute value of cerebral blood flow is the same as in normotensive individuals i.e. about 50 rnl. per 100 g. min. (Kety et al., 1948). Later it also became clear that the blood flow to the brain remained relatively constant with moderate blood pressure changes. This phenomenon, termed autoregulation, is mediated by calibre changes in the arterioles and small arteries of the brain. When the blood pressure falls, the arterioles dilate, thus preventing a reduction in cerebral blood flow, and when the blood pressure increases the arterioles constrict, thus preventing an increase in cerebral blood flow. Autoregulation is also present in hypertensive patients. There are, however, limits to the range of blood pressure over which cerebral blood flow remains constant. In normotensive man, and in the baboon, this range has been found to be approximately 60 to 140 mm. Hg mean arterial blood pressure. Below 60 mm. Hg autoregulatory vasodilatation is inadequate to compensate for the fall in blood pressure and, thereafter, cerebral blood flow decreases (Strandgaard et al., 1973; Fitch et al., 1975). The point at which blood flow falls is termed the lower limit of autoregulation of cerebral blood flow. Despite the reduction in brain blood supply occurring at this point, further slight reductions in blood pressure and, therefore, in cerebral blood flow, are required before the neurological symptoms of brain hypoperfusion, such as syncope, become manifest (Strandgaard et al., 1973). Scot. med, J., 1976, 21: 103