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Biomedical subjects

A E Doyle

Publications and source records attributed to A E Doyle.

At least 73 records · Page 4Linked to original sources

Assessment of vascular involvement in hypertension.

Vascular disease in hypertension is of two types. Disease of arterioles and small arteries affects predominantly the kidney and brain, and is due directly to the hypertension itself. Atheroma mainly affects large and medium size arteries and hypertension is only one of several factors involved in its causation. Clinical evidence of small vessel disease includes retinopathy, proteinuria and lacunar cerebral infarction. Assessment of atheromatous disease usually involves angiography. The recent development of non-invasive techniques such as digital subtraction angiography and ultrasound imaging promises to improve the assessment of vascular disease.

Arterioles↗

Methicillin-resistant Staphylococcus aureus in an Australian teaching hospital.

A survey was undertaken of all isolations of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) at a large Australian teaching hospital over a 12 month period. All methicillin-resistant isolations obtained from the Casualty and Outpatient clinics were from staff members or patients with recent hospital contact. Twenty per cent of all methicillin-resistant isolations from in-patients were from specimens taken within 2 days of the patient's admission. Each of these patients had had hospital contact within the previous 4 months and it is assumed that the majority of them reintroduced the organism into the hospital. Such patients may provide an important means by which infection control procedures are bypassed. Patients who were relatively more likely to become infected or colonized with methicillin-resistant than with methicillin-sensitive strains included the elderly and those with postoperative wound infections (especially after orthopaedic or vascular surgery), spinal injuries, peripheral vascular disease, chronic skin ulcers or chronic diseases of the respiratory or urinary tracts. Eleven per cent of MRSA wound isolates and 15 per cent of sputum isolates were associated with serious infections requiring specific treatment, emphasizing the ability of these strains to produce serious illness. A small proportion of staff and asymptomatic patients were found to harbour MRSA and the importance of these individuals in facilitating cross-infection requires further investigation.

Adult↗

Vascular prostacyclin and Goldblatt hypertensive rats.

Vascular prostacyclin production in Goldblatt hypertension was examined in one-kidney, one clip (1K, 1C) and two-kidney, one clip (2K, 1C) rat models. Vasodepressor responses to prostacyclin and nitroprusside correlated well with resting blood pressure in both groups of rats, but when measured as a percentage of resting blood pressure the responses did not differ significantly between hypertensive rats and the normotensive controls within each group. In contrast, the vasodepressor effects of arachidonic acid (1-3 mg/kg, i.v.) were much greater in the 1K, 1C rats than in their normotensive controls, but did not differ significantly between hypertensive 2K, 1C rats and sham-operated controls. The effects of arachidonic acid were virtually abolished by indomethacin (10 mg/kg, i.v.). The metabolism of [14C]-arachidonic acid was also studied in isolated aortae of both one- and two-kidney rats by high pressure liquid chromatography of extracts of the incubation mixture. [14C]-6-oxo-PGF1 alpha was the only prostanoid conversion product recovered from the incubations and significantly more of this metabolite was produced by aortic tissue from 1K, 1C rats than from normotensive controls. There was no difference in [14C]-6-oxo-PGF1 alpha production between 2K, 1C rats and controls. These results demonstrate an enhanced ability of vascular tissue from 1K, 1C hypertensive rats to convert exogenous arachidonate to vasodilator prostacyclin, but this is not evident in the two-kidney model. Although enhanced biosynthetic capacity for prostacyclin in the one-kidney model and spontaneously hypertensive rats does not lessen peripheral vascular resistance, it might reflect a fundamental disturbance in phospholipid metabolism which contributes to increased vascular resistance.

Animals↗

Failure of psychosocial stress to induce chronic hypertension in the rat.

The effect of psychosocial stress produced by aggregation in a special cage designed by Henry was investigated in three separate experiments using Wistar-Kyoto (WKY), Sprague-Dawley (SD) and F1 hybrids of the Japanese spontaneously hypertensive and Wistar-Kyoto (SHR-WKY F1) rats. Each aggregated group displayed typical 'stressed' behavioural disturbances. Adrenal hypertrophy, elevation of plasma renin activity and gastric erosions were noted in male aggregated SD rats; while adrenal enlargement, elevation of plasma noradrenaline and gastric erosions were found in male aggregated SHR-WKY F1 rats. Sustained hypertension, however, did not develop in any strain nor in any subgroup within each strain. Gastric erosions were also noted in isolated SD and SHR-SKY F1 rats suggesting that long term isolation of rats also induces stress. Isolated rats also remained normotensive throughout. Reduced haematocrit was found in both aggregated and isolated male SHR-WKY F1 rats suggesting increased plasma volume. We conclude that neither stress due to psychosocial disturbances nor that due to isolation produces chronic hypertension in the three strains of rat studied.

Adrenal Glands↗

Exchangeable sodium in renal hypertension in the rat.

Rats with two-kidney, one-clip hypertension (2K1C) have a marked rise in plasma renin activity (PRA) and, when drinking 0.9% NaCl as their sole source of sodium, have increased exchangeable and total body sodium levels. These changes are reversed by the administration of captopril. The one-kidney, one-clip (1K1C) model has no rise in PRA or increase in body sodium level after either an early or a late contralateral nephrectomy. The data indicate that hypertension in the 2K1C model is due to the high angiotensin levels in these animals. Activation of the renin-angiotensin system requires the presence of the contralateral kidney but is not the result of sodium loss from that kidney. The reason for activation of the renin-angiotensin system in the 2K1C hypertensive rat remains obscure.

Animals↗

Sodium intake and exchangeable sodium in hypertensive rats.

Exchangeable sodium, extracellular fluid volume and sodium intake were significantly higher in spontaneously hypertensive rats (SHR) than in normotensive controls. The increased exchangeable sodium was due to the expanded extracellular fluid sodium content. Two kidney one clip Goldblatt renal hypertensive rats develop thirst and high renin levels. When drinking saline the rats have markedly increased exchangeable sodium levels, but those drinking water did not. It is proposed that the exaggerated saline intake leads to a volume dependent component of the hypertension in both models. In the SHR both the salt appetite and the hypertension may be induced by angiotensin acting via central mechanisms.

Animals↗

Rapid eye movement (REM)-sleep during and after continuous infusion of the oxazoline derivate S3341: a comparison with clonidine.

The frequency and duration of rapid eye movement (REM)-sleep episodes were examined in normotensive rats during and after cessation of continuous infusion of either clonidine (10 micrograms/kg/h) or the oxazoline derivative S3341 (50 micrograms/kg/h) for 10 days. Both compounds abolished REM-sleep during the infusion. On cessation of the clonidine infusion there was a rebound increase in the frequency and duration of REM-sleep episodes. These episodes were associated with markedly exaggerated blood pressure fluctuations. On cessation of the S3341 infusion, the frequency and duration of REM-sleep episodes returned to control levels. Blood pressure responses were not different from controls. These post-infusion differences may be related to the greater degree of selectivity of S3341 for the alpha 2-adrenoceptor rather than the alpha 1-adrenoceptor subtype.

Animals↗

NHMRC workshop on non-pharmacological methods of lowering blood pressure. Sodium restriction.

Data on the effects of severe salt restriction suggest that some, but by no means all, patients with severe hypertension respond well. The effects of less severe salt restriction on blood pressure are inconclusive, but suggest that diuretics are more effective than dietary salt restriction in reducing blood pressure. The possibilities of variation between individuals in sensitivity to sodium intake has not been adequately explored.

Blood Pressure↗

Effect of DOCA-salt on angiotensin dependency and surgical reversal of hypertension in two-kidney, one clip renal hypertensive rats.

The development of hypertension in two-kidney, one clip renal hypertensive rats (2K, 1C RHR) was not altered by treatment with DOCA and saline solution as drinking fluid for two months of observation. However, the administration of DOCA and salt suppressed plasma renin activity (PRA), the renal renin content (RRC) of the clipped kidney and the response to a single oral dose of captopril (10 mg/kg). The weight of the contralateral kidney was increased by the administration of DOCA-salt, while that of the ischaemic kidney was not changed. The withdrawal of DOCA-salt treatment restored the PRA and the effects of captopril to a similar degree to the non-treated group. The acute hypotensive effects of captopril were reduced on the 10th week compared with the 7th week after renal arterial constriction in 2K, 1C RHR. The fall in blood pressure induced by captopril significantly correlated with the initial PRA both in the 7th and 10th week after clipping. There was a significant correlation between PRA and RRC of the clipped kidney. Rats previously treated with DOC-salt had either removal of the contralateral kidney with removal of the clip from the ischaemic kidney, or removal of the ischaemic kidney. Blood pressure fell to normal levels in the unclipped group and in the nephrectomy group, but the fall in the latter group was transient and within two weeks had risen to significantly higher levels than in the unclipped group. It is concluded that structural vascular change following DOC-salt hypertension is insufficient to cause persisting hypertension except when it occurs in the renal circulation.

Animals↗

Impaired angiotensin-induced drinking in spontaneously hypertensive rats.

The drinking response during the 30 minutes following intracerebro-ventricular injection of angiotensin II (AII) (1 to 200 ng) was compared in male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto control rats (WK). SHR drank significantly less than WK at the 10, 50 and 100 ng doses. In contrast, responses to intracerebroventricular carbachol and intraperitoneal hypertonic saline were not different between SHR and WK. These agents are believed to induce drinking by mechanisms independent of angiotensin. Binding of I125-labelled AII to particles prepared from the hypothalamus, thalamus, septum and midbrain (HTSM) region was measured in one month old male and two month old female SHR and their respective age matched WK controls. No differences were found in binding between SHR and WK of either sex. These data demonstrate an impairment of drinking responses in the SHR which seem to be specific for angiotensin. This finding supports the hypothesis that the CNS angiotensin system might be abnormal in these animals.

Angiotensin II↗

In vivo comparison of three orally active inhibitors of angiotensin-converting enzyme.

This study was designed to compare the activity of three structurally different drugs (SQ 14225 [captopril], SA 446 and MK 421) as inhibitors of angiotensin I-converting enzyme in vivo and to compare their effects on blood pressure in spontaneously hypertensive rats and one clip, two kidney renal hypertensive rats. All the three drugs were potent, orally effective converting enzyme inhibitors. The relative durations of their actions as inhibitors of angiotensin-converting enzyme, from longest to shortest, were as follows: MK 421, SQ 14225 and SA 446. MK 421 appears the most potent on a molar basis. In renal hypertensive rats the drugs appeared equipotent, although the duration of action of MK 421 was prolonged and SA 446 shorter than that of SQ 14225. SA 446 was less effective than the other two compounds in spontaneously hypertensive rats.

3-Mercaptopropionic Acid↗

Dissociation of dipsogenic and pressor responses to chronic central angiotensin II in rats.

Chronic intracerebroventricular (icv) infusion of angiotensin II (ANG II) (6 micrograms/h) in rats resulted in a sustained 70-mmHg rise in blood pressure during 7 days of treatment. A marked dipsogenic response preceded the maximal rise in blood pressure, peaked at 24 h, and returned to control by the 5th day. Urinary sodium excretion rose on the 1st day of infusion but thereafter was not different from that of vehicle-infused rats. ANG II-infused rats showed a small but significant kaliuresis, a fall in serum osmolality (5.5 mosmol/kg), but no change in plasma Na+, K+, or glucose. Rats infused with the same dose of ANG II intravenously showed a small, 8-mmHg rise in blood pressure, but none of the changes noted after icv ANG II. Plasma renin activity was suppressed in rats infused with ANG II by both routes. We conclude that the pressor, dipsogenic, and renal excretory effects of icv ANG II are mediated centrally and cannot be explained by leakage of the peptide into the systemic circulation. Furthermore, the pressor and dipsogenic effects of ANG II become clearly dissociated during chronic icv infusion.

Angiotensin II↗

Exchangeable sodium, plasma renin activity and blood pressure changes during the development of 2 kidney 1 clip hypertension, and after subsequent contralateral nephrectomy.

Sequential changes in exchangeable sodium, fluid intake, blood pressure and plasma renin activity were measured in 2K1C hypertensive rats during the development of severe hypertension. Exchangeable sodium was measured by the equilibration of the rats' exchangeable sodium with radioactive saline. In rats drinking saline, both PRA and exchangeable sodium levels increased as hypertension developed, and captopril induced large falls in blood pressure. Subsequent removal of the contralateral kidney reduced PRA, but did not alter exchangeable sodium or blood pressure. Captoril had no effect on blood pressure. It is concluded that the rise in PRA in 2K1C hypertension depends on the presence of the contralateral kidney, but occurs in the absence of sodium depletion.

Animals↗