Biomedical subjects

K M Denton

Publications and source records attributed to K M Denton.

27 records · Page 2Linked to original sources

PubMed1990

Angiotensin II and the maintenance of GFR and renal blood flow during renal artery narrowing.

The time course of the renal blood flow and GFR responses to narrowing of the renal artery in conscious dogs is reviewed. The initial response to this threat to renal perfusion is renal vasodilatation, but within minutes a secondary vasoconstriction mediated by angiotensin II begins to develop. Angiotensin II-mediated contraction of mesangial cells is also demonstrable, but this does not apparently reduce the filtration surface area of the glomerular capillaries. The intrarenal effects of angiotensin II restore GFR back to normal within one to two weeks, by which time circulating plasma angiotensin II levels are no longer elevated. In contrast to its effects on GFR, angiotensin II has minimal effects on renal blood flow after stenosis. This may be because, (i) blood flow is mainly determined by the hydraulic resistance of the stenosis; (ii) renal vasoconstriction has relatively little effect on flow due to the particular hemodynamic properties of the stenoses, and (iii) a major site of action of angiotensin II may be within the glomerulus. Thus angiotensin II has a homeostatic role in the maintenance of GFR during renal artery narrowing and one component of this role may involve mesangial contraction.

Angiotensin II↗

PubMed1989

Renal venous wedge pressure in renal wrap hypertension in rabbits.

1. Renal cellophane wrapping to produce hypertension causes thickening of the capsule of the kidney. To determine whether this compresses the kidney, deep renal vein wedge pressure was measured as an estimate of tissue pressure in anaesthetized rabbits 1 month after cellophane wrapping (n = 5) or a sham operation (n = 3). 2. Renal vein wedge pressure was 18.3 +/- 2.0 mmHg in hypertensive rabbits and 8.4 +/- 1.1 mmHg in the sham-operated rabbits. 3. Arterial pressure was raised or lowered with angiotensin II or glyceryl trinitrate, respectively. Arterial and wedge pressures were approximately linearly related and, at any given arterial pressure, wedge pressure was approximately 8 mmHg higher in the cellophane-wrapped kidney than in the kidney of the sham-operated group. 4. These results, showing that renal wedge pressure is elevated in renal wrap rabbits, indicate that the kidneys are compressed, probably by the thickened renal capsule. This may explain the increased renal vascular resistance seen in this form of hypertension.

Angiotensin II↗

PubMed1989

Renal effects of atrial natriuretic peptide in conscious rabbits with renal wrap hypertension.

Atrial natriuretic peptide (ANP, 2 micrograms/min) was infused intravenously into rabbits four weeks after renal wrap or sham operation. Mean arterial pressure (MAP) averaged 132 +/- 4 mmHg in the renal wrapped rabbits and 89 +/- 3 mmHg in the sham rabbits, and glomerular filtration rate (GFR) was significantly lower in the hypertensive rabbits (6.2 +/- 1.0 ml/min) than in sham rabbits (8.9 +/- 0.7 ml/min). In sham rabbits, ANP caused a significant diuresis, natriuresis and increase in GFR. Enalapril pretreatment blunted these responses. In the hypertensive rabbits, ANP reduced mean arterial pressure but did not cause significant diuresis or natriuresis or change in GFR. Enalapril pretreatment did not significantly alter this response to ANP. In separate experiments, nitroprusside was infused to lower arterial pressure in hypertensive rabbits by a similar amount to that achieved with ANP and this reduced GFR, sodium and urine excretion rates. Thus ANP maintained GFR and sodium excretion in hypertensive rabbits compared to an equihypotensive dose of nitroprusside. In summary, ANP did not cause natriuresis or diuresis in renal wrapped kidneys at a dose which was effective in normal kidneys, but did maintain GFR, sodium and water excretion rates, compared to an equally hypotensive dose of nitroprusside.

Animals↗

PubMed1988

Renal and systemic vascular conductances in renal wrap hypertension in rabbits.

The contribution of renal vascular conductance to the fall in total peripheral conductance during the development of renal wrap hypertension was determined in conscious rabbits. Measurements were made 28 days after renal wrap (n = 9) or sham operation (n = 8). Blood pressure was about 50 mmHg higher in the wrapped group as compared to the sham-operated group. This was due to a fall in total peripheral conductance of about 42%. Cardiac output was not significantly different between wrap and sham groups. Renal vascular conductance was 0.42 ml/min per mmHg lower in the wrap compared to the sham-operated group (P less than 0.001). Total peripheral conductance was 3.93 ml/min per mmHg lower in the wrap compared to the sham group (P less than 0.01). The reduction in renal vascular conductance in wrapped rabbits, which is probably due to compression caused by the thickening renal capsule, accounts for about 10% of the fall in total peripheral conductance. We suggest that this mechanically induced reduction in renal conductance is involved in the initiation and maintenance of the hypertension, but is only a minor contributor to the overall change in blood pressure.

Animals↗

PubMed1988

Decreased renal responses to atrial natriuretic peptide in renal wrap hypertension.

1. The effects of atrial natriuretic polypeptide (ANP) on renal function were examined in renal wrap hypertensive rabbits and sham operated rabbits. 2. ANP (2 micrograms/min) induced hypotension, but did not produce significant diuresis, natriuresis or change in the glomerular filtration rate (GFR) in renal wrap hypertensive rabbits (n = 8). 3. In sham operated normotensive rabbits (n = 4), ANP induced significant diuresis (230%) and increased GFR by about 40%. 4. Thus, ANP was markedly less effective in the impaired kidneys of renal wrapped rabbits than in normal kidneys.

Animals↗

PubMed1987

Renal actions of angiotensin II in renovascular hypertension.

In renal artery stenosis severe enough to cause hypertension, angiotensin II maintains glomerular filtration rate (GFR) both in the initial high renin phase of hypertension and later when plasma levels are normal. Angiotensin II also maintains GFR in less severe stenosis, which does not cause hypertension. This homeostatic action of angiotensin II to maintain GFr has minimal effects on blood flow. In renal-wrap hypertension, plasma renin levels are elevated for longer than after renal artery stenosis, but in other respects this initial phase of the hypertension is similar to that after renal artery stenosis. GFR is reduced, the rate of development of hypertension is accelerated by angiotensin II, and angiotensin II maintains the glomerular filtration fraction. Renal resistance is markedly increased owing to both compression of the kidney by the hypertrophying renal capsule and to angiotensin II. Thus angiotensin II apparently plays a primarily homeostatic role in renovascular hypertension to maintain glomerular ultrafiltration. It is suggested that the angiotensin II may be formed intrarenally and may act on sites other than resistance blood vessels.

Angiotensin II↗

PubMed1986

Effect of renal denervation on the development of cellophane-wrap hypertension in rabbits.

The development of hypertension in rabbits with bilateral cellophane wrapping of the kidneys was studied in animals with and without surgical denervation of the kidneys. Mean arterial pressure was measured before and 14 and 28 days after surgery. After 14 and 28 days of wrapping, mean arterial pressure had increased 12 +/- 3 mmHg and 31 +/- 3 mmHg in rabbits with innervated kidneys and 7 +/- 2 mmHg and 26 +/- 2 mmHg in rabbits with denervated kidneys, respectively. The increases in arterial pressure were significantly less in the denervated animals. In sham wrap animals, renal denervation also resulted in significantly lower arterial pressure than in sham wrap+sham denervated rabbits. Noradrenaline concentration of denervated kidneys averaged only 4% of that measured in kidneys subjected to sham denervation. The results show that renal denervation slightly attenuated the degree of hypertension developed following renal wrapping. Since renal denervation produced a similar small decrease in arterial pressure in normotensive rabbits it is suggested that the effect is non-specific and probably due to loss of efferent renal sympathetic nerves.

Animals↗

PubMed1983

Renal blood flow and glomerular filtration rate in renal wrap hypertension in rabbits.

Serial measurements of mean arterial pressure and glomerular filtration rate (GFR) were made in rabbits before and 10, 28 and 56 days after bilateral renal cellophane wrap (n = 8) or sham operation (n = 6). No significant changes were seen 10 days after renal wrap, but by 28 days GFR was reduced by 50 +/- 3% and mean arterial pressure had risen by 42 +/- 5 mmHg. No significant further changes occurred over the subsequent month. Changes in plasma renin activity after renal wrapping were not significantly different to those seen after sham operation. In a separate series of experiments, renal extraction ratio of para-aminohippurate (PAH), 28 days after renal wrap, averaged 63 +/- 4% (n = 6) compared to 83 +/- 2% (n = 5) after sham operation. Calculated renal blood flow of the hypertensive rabbits was only about 40% of that in the sham operated rabbits. Thus large reductions in GFR, renal blood flow and PAH extraction ratio occurred following bilateral renal wrapping and these changes may reflect compression of the kidney by the cellophane induced fibrous capsule. These reductions occurred concomitantly with the rise in arterial blood pressure.

Animals↗

PubMedDate not supplied

Role of angiotensin II in renal wrap hypertension.

The role of angiotensin II in the development of renal wrap hypertension was studied in rabbits that underwent either bilateral renal cellophane wrap or sham operation. In half the rabbits, angiotensin II production was blocked by continuous administration of enalapril. Four weeks after renal wrapping, mean arterial pressure had risen by 48 +/- 5 mm Hg in untreated rabbits, but by only 25 +/- 4 mm Hg in enalapril-treated rabbits (p less than 0.01). Similar differences were also measured 6 weeks after wrapping. In untreated rabbits, plasma renin activity had increased fourfold 4 and 6 weeks after renal wrapping. There were no significant changes in blood pressure or plasma renin activity following sham operation. Compared with that in sham-operated rabbits, renal blood flow was reduced by 60% in the untreated rabbits 4 weeks after wrapping but by only 30% in the enalapril-treated wrapped rabbits (p less than 0.05). Renal vascular resistances were 5.5 +/- 1.7 mm Hg . ml-1 . min-1 and 1.2 +/- 0.1 mm Hg . min . ml-1 in the untreated wrapped and sham-operated rabbits respectively and 1.9 +/- 0.4 mm Hg . min . ml-1 and 0.8 +/- 1 mm Hg . min . ml-1 in the enalapril-treated wrapped and sham-operated rabbits. Renal wrapping did not alter filtration fraction in untreated rabbits, but markedly reduced it in enalapril-treated rabbits. These results suggest that angiotensin II had two major effects in rabbits after bilateral renal wrapping: it contributed substantially to the increase in blood pressure and caused renal vasoconstriction, primarily at a postglomerular site.

Angiotensin II↗