Biomedical subjects

J A Angus

Publications and source records attributed to J A Angus.

167 records · Page 10Linked to original sources

PubMedDate not supplied

Intrarenal action of angiotensin II in restoring renal artery pressure after acute renal artery stenosis.

1. The renal artery of conscious dogs was acutely narrowed over 30 s to reduce renal artery pressure distal to the stenosis to 40 mmHg and the stenosis was maintained for 1 h. The distal renal artery pressure was rapidly restored to a plateau slightly below pre-stenosis values within 10--15 min. Rises in systemic blood pressure and plasma renin activity were small and transient. 2. This restoration was an active process, mediated by the intrarenal effects of angiotensin II (AII), since it was greatly diminished or abolished when the renal artery was narrowed in the presence of angiotensin I-converting enzyme inhibitor or angiotensin receptor antagonist (1-Sar-8-Ile AII). However, it was not diminished by 'total' autonomic effector blockade. 3. This angiotensin II-mediated restoration of renal artery pressure may be of homeostatic significance for the maintenance of glomerular filtration rate.

Angiotensin II↗

PubMedDate not supplied

Structural determinants of vascular resistance properties in hypertension. Haemodynamic and model analysis.

The average internal radius (ri) of the resistance vessels of the hindquarter (HQ) bed was narrower in renovascular and genetic hypertension than in normotensive controls. The narrowing was approximately uniform over the full range of vasomotor tone, which accounted for the bed's property as an 'amplifier' of vascular resistance (R) (increased slope (S) of the dose-R response curve) and for the elevated R at maximum dilatation (Rmin). In the model we examined the effects on the dose-R curve parameters of altering wall/internal radius (w/ri) ratio, ri and wall 'stiffness' one at a time, whilst the others were held constant: only narrowing of ri led to increases in both S and Rmin; with hypertrophy alone, S increased but Rmin was reduced, whilst increased wall stiffness increased Rmin but lowered S. Thus, for hypertrophy to be associated with rises of both S and Rmin, it must be linked to lumen narrowing, to increased wall stiffness, or to both. Preferential deposition of new material towards the lumen will link hypertrophy to narrowing. It has been suggested that narrowing can occur without hypertrophy ('remodelling'). In the model an increase of only 1-2% WV was required to produce rises in w/ri of congruent to 30-50% when associated with congruent to 10-15% reduction in ri, which is close to the limit of detection. From the literature, the sites of greater narrowing in hypertension extend down to small arteries and large arterioles. The rise in BP upstream from those sites, due to the vascular amplifier, offsets the down-stream effects of vascular narrowing on blood flow and this negative feedback system helps to maintain elevation of BP at a stable level. We also examined developmental rise in R between 4 and 50 weeks, which affected SHR and WKY in the same proportion: structural factors (vascular length of larger arteries, 'rarefaction' of arterioles and capillaries) accounted for only about half the rise in R, and the remainder was probably due to developmental changes in muscle function.

Animals↗

PubMedDate not supplied

Wall thickness to lumen diameter ratios of arteries from SHR and WKY: comparison of pressurised and wire-mounted preparations.

Passive properties (diameter, wall-to-lumen ratio and axial length) of small mesenteric arteries from SHR and WKY rats were measured with the artery segments cannulated and pressurised, or mounted on wires in a myograph. The measurements were made with a range of distending pressures (or calculated equivalent distending pressures when wire-mounted) from 0 to 180 mm Hg. The axial length of artery segments increased with increasing distending pressure when cannulated, but not when wire-mounted. The axial extension was greater for arteries from WKY (up to 105%) than for arteries from SHR (up to 65%). The arteries from SHR had significantly smaller diameters and greater wall-to-lumen ratios than the arteries from WKY. However, the diameters calculated for the arteries when wire-mounted were less than the measured diameters, and the wall-to-lumen ratio was always greater when wire-mounted than when cannulated because of the underestimated diameter and the absence of axial extension. Wall-to-lumen ratios decreased with increased distending pressure; values at 180 mm Hg were only 18 and 25% of those at 0 mm Hg for WKY and SHR arteries, respectively. The large degree of variability of wall-to-lumen ratios obtained from the two different preparations and the large range of values that are obtained from a single artery at different distending pressures must call into question the validity of characterising vascular hypertrophy by any single estimation of this parameter.

Animals↗

PubMedDate not supplied

Alpha 1- and alpha 2-adrenoceptor-mediated pressor responses: are they differentiated by calcium antagonists or by functional antagonism?

We investigated the effect of cardiovascular depression on the pressor responses to the alpha 1-adrenoceptor selective agonist methoxamine, and the alpha 2-adrenoceptor selective agonist B-HT 920 in anesthetized ganglion-blocked rats. The calcium channel blocking drug nifedipine preferentially inhibited the effect of B-HT 920, as has been reported by other authors. Lowering the starting blood pressure by hemorrhage, by nitroprusside infusion, or by additional pentobarbitone also preferentially inhibited the pressor effect of B-HT 920. These selective effects of vascular depression on B-HT 920 are consistent with predicted interactions between functional antagonists and a partial (low-efficacy) agonist. This was tested in part by reducing the maximum effect of methoxamine by phenoxybenzamine treatment. Under these conditions, methoxamine behaved like B-HT 920 in that it was sensitive to inhibition by nitroprusside infusion. By analogy, the vasodepressive effect of calcium channel blocking drugs could be responsible for the preferential inhibition of the vasoconstrictor responses to alpha 2-adrenoceptor agonists. It is concluded that a differential reliance on influx of extracellular Ca2+ by alpha 1- and alpha 2-adrenoceptors may not be the only explanation of the selective effect of calcium channel blocking drugs.

Animals↗

PubMedDate not supplied

Interaction of epoprostenol (PGI2) with vasoconstrictors on diameter of large coronary arteries of the dog.

The platelet release products thromboxane A2 (TxA2) and serotonin (5-HT) might contribute to coronary vasoconstriction in humans. We have examined the effects of a TxA2-like analogue (U46619), 5-HT, and epoprostenol (PGI2) on the left anterior descending coronary artery of the dog. Changes in diameter were measured by sonomicrometry during perfusion of the vessel with blood from a support dog, at constant flow and distal resistance. Intra-arterial infusions of 5-HT (0.01-1 mumol/L) and U46619 (0.003-0.1 mumol/L) reduced external diameter of the artery (about 2.0 mm) by 0.12 mm and 0.16 mm, respectively. Intra-arterial PGI2 (0.01-0.1 mumol/L) increased the diameter of the artery (by 0.08 mm) and reduced blood pressure of the support dog (by 23 mm Hg), but did not significantly (p greater than 0.05) reduce the vasoconstrictor effects of either 5-HT (0.3 mumol/L) or U46619 (0.1 mumol/L) infused simultaneously. Indomethacin (5 mg/kg i.v.) doubled the direct dilator effect of PGI2, and increased the sensitivity of the artery to 5-HT (by 11.5-fold) and to U46619 (by 2.8-fold). After indomethacin infusion, intra-arterial PGI2 (0.1 mumol/L) reduced the constriction induced by continuous infusion of 5-HT or U46619. These data suggest that PGI2 may be of limited usefulness in preventing constriction of large coronary vessels because it causes hypotension. However, endogenous PGI2 produced by the coronary vessels or pericardium may modulate the influence of coronary vasoconstrictors, and these tissues are therefore potential targets for PGI2-releasing drugs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗