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Biomedical subjects

J O Davis

Publications and source records attributed to J O Davis.

At least 37 records · Page 2Linked to original sources
PubMed1983

Splanchnic and renal contributions to circulatory homeostasis in sodium depletion.

Chronic sodium depletion is a state of reduced cardiac output in which the renin-angiotensin system is actively involved in maintenance of mean arterial blood pressure (MAP). Angiotensin II (ANG II) blockade with saralasin is known to produce renal vasodilation and a decrease in MAP in the sodium-deplete dog. In this study conscious trained dogs with chronic indwelling catheters were sodium depleted with diuretics plus a low sodium diet. Hepatic blood flow (HBF) and renal blood flow (RBF) were determined concurrently by the clearances of bromosulfophthalein and p-aminohippurate, respectively. When compared with the sodium-repleted state, the depleted dogs had reduced HBF with no change in MAP or RBF. In addition, the hepatic renin clearance and percent hepatic renin extraction were reduced. When saralasin was given intravenously to the depleted dogs, the response was a decrease in MAP with a concurrent decrease in both renal and splanchnic vascular resistances. The increased plasma renin activity during saralasin was accompanied by increased hepatic renin extraction but no significant rise in hepatic renin clearance. Saralasin also resulted in a large decrease in the urinary excretion of prostaglandin E2. This study provides evidence that increased plasma ANG II levels are responsible for the increased splanchnic vascular resistance during chronic sodium depletion.

Angiotensin II↗
PubMed1983

Effects of indomethacin in conscious dogs with experimental high-output heart failure.

The role of renal prostaglandins in the control of renin release and renal hemodynamic function (RHF) was studied in conscious dogs with a surgically created infrarenal aortocaval fistula, a model of high-output heart failure (HOHF). In series 1 during acute cardiac failure, indomethacin administration produced striking reductions in RHF but failed to alter the high level of plasma renin activity (PRA). In series 2, administration of indomethacin to dogs with chronic HOHF also resulted in pronounced decrements in RHF in spite of normal levels of PRA. Studies of individual animals with meclofenamate in both series 1 and 2 confirmed the findings with indomethacin with one exception; in one dog with chronic severe HOHF a very high level of PRA was present initially and fell 44% after meclofenamate. These observations indicate that in the acute and chronic phases of HOHF prostaglandins are involved in the maintenance of renal blood flow and glomerular filtration rate but do not play an essential role in the control of renin release.

Animals↗
PubMed1983

A denervated nonfiltering kidney preparation in the rat: a model for study of renin release.

To examine the role of the renal vascular receptor in the control of renin secretion in the rat, a denervated, nonfiltering kidney model (DNFK) was developed. The left kidney was subjected to a 2-hr period of total renal ischemia followed by ureteral ligation and section Denervation was accomplished by stripping all visible nerves and painting the renal vessels with 5% phenol. Forty-eight hours later lissamine green dye was injected iv and failed to appear in either the cortical or medullary tubules, indicating that glomerular filtration had ceased. Histological study of these kidneys revealed diffuse tubular necrosis with extensive intratubular cast formation. Norepinephrine content of the DNFK was reduced 91% compared to the contralateral normal kidney (P less than 0.001). In another group of anesthetized rats with a single DNFK, 15 min of suprarenal aortic constriction (SAC) increased plasma renin activity (PRA) from 3.4 +/- 0.6 to 11.5 +/- 1.6 ng AI/ml/hr; in a time control series, PRA was unchanged. To exclude the influence of adrenal catecholamines in this response, bilateral adrenalectomy was performed in a separate group of animals with a DNFK. In this series, SAC also markedly increased PRA. The present data indicate that in the rat the macula densa, the renal nerves, and adrenal catecholamines were not essential for the hyperreninemia induced by a reduction in renal perfusion pressure.

Animals↗
PubMed1982

Historical perspectives on the renin-angiotensin-aldosterone system and angiotensin blockade.

Advances leading to recognition of the relation of the renin-angiotensin system to aldosterone include: (1) development of analytic techniques for measuring aldosterone, (2) discovery of an aldosterone-stimulating factor in circulating plasma, (3) the finding that a potent aldosterone-stimulating factor is secreted by the kidney, (4) evidence that synthetic angiotensin II increases aldosterone secretion, (5) fractionation of crude kidney extracts and the finding that aldosterone-stimulating factor is renin, (6) the observation that high plasma renin activity occurs in secondary aldosteronism, and (7) recognition that the renin-angiotensin-aldosterone system occurs in congestive heart failure and in renovascular and malignant hypertension. The early use of blocking agents for the renin-angiotensin system is described along with the landmarks of progress. These include the observations that: (1) arterial pressure decreases in experimental renovascular hypertension in response to angiotensin blockade, (2) angiotensin provides important support for arterial pressure in low cardiac output states including congestive heart failure, (3) the kidney participates in this important compensatory mechanism, and (4) cellular receptors for angiotensin are present in the two inner zones of the adrenal cortex.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Effects of prostacyclin on hepatic vasculature and metabolism of renin in conscious dogs.

Prostaglandins have been implicated as important regulators of vascular resistance during high-renin states, and they act as potent stimuli for renin release. This study examines the effects of prostacyclin (PGI2) in conscious sodium-replete and -deplete dogs on the hepatic vasculature and on hepatic function and their role in determining the level of arterial plasma renin activity (PRA). Concurrent measurements of kidney function were made for comparison. Conscious trained dogs with chronic indwelling catheters were given intravenous infusions of PGI2. With a low dose of PGI2 (2 x 10(-8) g . kg-1 . min-1) hepatic blood flow increased while splanchnic vascular resistance fell. With a higher dose (8 x 10(-8) g . kg-1 . min-1) mean arterial pressure fell, and both hepatic and renal blood flow increased while splanchnic and renal resistances fell. The PGI2 infusion was accompanied by an increase in PRA. In both sodium-replete and -deplete animals the increases in PRA were accompanied by proportional increases in the hepatic extraction of renin and increases in the hepatic clearance of renin. Small but significant differences were found in the responses of sodium-replete and -deplete animals to PGI2 infusion. These results demonstrate that PGI2 has a potent influence on both the splanchnic and renal vasculatures and the hepatic clearance of renin and thus the role of the liver in determining hyperreninemia.

Animals↗
PubMed1982

Volume and vasoconstriction in experimental renovascular hypertension.

An analysis is presented of volume and vasoconstrictor factors in experimental renovascular hypertension. Volume expansion and increased cardiac output produced by renal retention of salt and water are not essential for chronic renovascular hypertension to develop. When volume expansion and increased cardiac output do occur, however, it appears that the increased cardiac output contributes directly to the hypertensive process without triggering myogenic alterations in peripheral resistance predicted by the whole-body autoregulation theory of hypertension. Activation of the renin-angiotensin vasoconstrictor mechanism is not essential for either the development or the maintenance of chronic one-kidney renovascular hypertension in either the dog or the rat. In experimental two-kidney renovascular hypertension, a clear species difference is apparent. In the two-kidney hypertensive dog, the angiotensin pressor mechanism appears to play only a transient role lasting about 1 wk. In the two-kidney Goldblatt hypertensive rat, however, both the development and the maintenance of the hypertension are angiotensin-dependent, at least for a 4- to 6-wk period. When both the volume component and the renin-angiotensin vasoconstrictor component were deleted in one-kidney rats by sodium depletion and chronic SQ 14225 administration, renal artery stenosis failed to produce chronic renovascular hypertension. It is concluded that the pathogenesis of chronic renovascular hypertension requires either volume expansion produced by renal salt and fluid retention or expression of the renin-angiotensin vasoconstrictor mechanism.

Animals↗
PubMed1981

Effects of indomethacin in dogs with acute and chronic renovascular hypertension.

This study examines the role that prostaglandins play in both the developmental and chronic phases of renovascular hypertension. Two 5-mg/kg doses of indomethacin were given to conscious dogs with renal denervation and receiving propranolol during the acute and chronic phases of one-kidney (1-KHT) and the acute phase of two-kidney (2-KHT) renovascular hypertension. Indomethacin produced striking reductions in plasma renin activity from the high level observed during the acute phase of both 1-KHT and 2-KHT. However, plasma renin activity failed to return to normal, and the hypertensive level of pressure decreased only slightly. In the chronic 1-KHT dogs, indomethacin did not lower plasma renin activity or mean arterial blood pressure unless plasma renin activity was elevated above the normal level. Also, indomethacin failed to alter renal function during the acute phase of 1-KHT but effective renal plasma flow fell during chronic 1-KHT. These results suggest that, in the dog, renal prostaglandins are involved in the pathogenesis of both acute 1-KHT and 2-KHT, whereas the role of renal prostaglandins in the regulation of arterial pressure appears to be negligible in chronic 1-KHT except during superimposed sodium depletion or severe hypertension. The data indicate that prostaglandins are involved in renovascular hypertension in the dog only under conditions where plasma renin activity is elevated. It is suggested that the release of renin after renal artery constriction is mediated by the vascular receptor that is at least partially independent of renal prostaglandin synthesis.

Animals↗
PubMed1981

Sodium and angiotensin in the pathogenesis of experimental renovascular hypertension.

The effects of simultaneous angiotensin blockade and sodium depletion on the development of one-kidney renovascular hypertension were studied in rats. In sodium-replete rats, systolic blood pressure (SBP) increased from 102 +/- 2 to 153 +/- 11 mmHg by the 12th day after unilateral nephrectomy and subsequent partial occlusion of the renal artery with a 0.22-mm silver clip. When changes in body fluid volume were minimized by sodium restriction in a second group of rats, the increase in SBP from 98 +/- 4 to 149 +/- 7 mmHg after clipping was not different from that in sodium-replete animals. Inhibition of the angiotensin-converting enzyme with SQ 14,225 during sodium restriction prevented the SBP from increasing above 101 +/- 3 mmHg by the 12th day after nephrectomy and clipping. Once SQ 14,225 administration was discontinued, SBP rose significantly to 148 +/- 5 mmHg within 5 days. Because previous studies have shown that neither sodium depletion nor angiotensin blockade alone prevented the development of one-kidney renovascular hypertension, it is concluded that the increase in blood pressure resulting from renal artery constriction and contralateral nephrectomy was prevented only by suppression of both the renin-angiotensin system and body fluid volume.

Angiotensin II↗
PubMed1981

Adrenergically induced renin release in conscious indomethacin-treated dogs and rats.

To investigate the role of endogenous prostaglandins in renin release stimulated via adrenergic pathways, isoproterenol, norepinephrine (NE) and NE in the presence of phentolamine (PTA) were infused into conscious sodium-replete rats and dogs. Isoproterenol (1 microgram.kg-1.min-1) infusion into intact rats increased plasma renin activity (PRA) eightfold. AFter pretreatment with the prostaglandin (PG) cyclooxygenase inhibitor indomethacin (5 mg/kg), isoproterenol increased PRA 16-fold. In dogs, isoproterenol (0.4 microgram.kg-1.min-1) increased PRA six-fold before indomethacin and 11-fold during PG inhibition. Infusion of NE into both rats (250 ng.kg-1.min-1) and dogs (1 microgram.kg-1.min-1) failed to increase PRA before indomethacin, but during inhibition of PG synthesis NE increased PRA in both species. During partial alpha-adrenergic blockade with PTA in dogs, PTA alone increased PRA by 38% and NE given during PTA infusion increased PRA further both before indomethacin by twofold and during PG inhibition by fivefold. In rats given NE during PTA infusion, PRA increased only after indomethacin injection. Additionally, in dogs the renin responses to these adrenergic agents were even greater after indomethacin administration than before the drug. These results in both conscious rats and dogs give no indication that renal prostaglandins mediate the renin response to adrenergic stimulation.

Animals↗
PubMed1981

Effects of indomethacin, renal denervation, and propranolol on plasma renin activity in conscious dogs with chronic thoracic caval constriction.

The role of renal prostaglandins and the adrenergic nervous system in the control of renin release was studied in conscious dogs with thoracic caval constriction. Indomethacin reduced plasma renin activity (PRA) in intact animals with thoracic caval constriction by 43% but failed to change PRA after surgical renal denervation and during chronic propranolol administration; adrenergic blockade reduced the initial control level of PRA before indomethacin from 15 to 4 ng angiotensin I/ml per hr. Renal hemodynamic function was markedly reduced by indomethacin both before and after adrenergic blockade. These observations indicate that prostaglandins are involved in the control of renin release, but they appear to have a more important role in the control of renal arterial resistance. The adrenergic nervous system also plays a role in the hyperreninemia of caval constriction and, possibly, a greater role than the renal prostaglandins. In the first experimental design, surgical renal denervation and daily oral propranolol administration in dogs with caval constriction reduced PRA to normal in two of seven dogs and a natriuresis occurred. In four of the five remaining animals, PRA fell, but not to normal, and renal sodium excretion failed to increase. In a second experimental design, the kidneys were denervated and propranolol was given before the dogs were subjected to caval constriction and propranolol was continued for 5 days; PRA increased markedly, sodium retention occurred, and ascites formed. Under these circumstances, compensatory mechanisms secondary to caval constriction led to increased PRA in spite of adrenergic blockade.

Animals↗
PubMed1980

Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs.

We studied the control of renin release and renal hemodynamic function by administering prostaglandin synthetase inhibitors to conscious sodium-depleted dogs with blockade of the adrenergic nervous system induced by bilateral renal denervation and propranolol administration. Indomethacin (10 mg/kg) reduced plasma renin activity (PRA) by 59% from a high sodium-depleted value, but PRA was still 3 times the normal sodium-repleted level. Arterial pressure, CCr, CPAH, urine flow, and potassium excretion fell strikingly. Similar results were obtained with meclofenamate. When SQ 14,225 was given to another group of conscious, sodium-depleted dogs with adrenergic nervous system blockade, PRA increased from the high sodium-depleted level of 5.7 to 29.3 ng of Angiotensin I (AI)/ml per hour; indomethacin (10 mg/kg) appeared to reduce PRA (0.05 less than P less than 0.1) but to only 12.1 ng of AI/ ml per hour, which is 17 times the normal level. This high level of PRA after blockade of the adrenergic nervous system and injection of indomethacin suggests that important mechanisms other than norepinephrine and renal prostaglandins control renin release; it is proposed that both the renal vascular receptor and the macula densa are involved. The marked decreases in CCr and CPAH in response to indomethacin emphasize the important role of renal prostaglandins in the control of renal hemodynamic function during sodium depletion.

Animals↗
PubMed1980

Renal prostaglandins, renin release, and renal hemodynamic function in high renin states.

Renal prostaglandins play a role in the control of renin release during chronic sodium depletion, during the acute phase of renovascular hypertension and in experimental low output heart failure in conscious dogs. However, with marked inhibition of the renin-angiotensin system, the adrenergic nervous system and the renal prostaglandins, PRA was still 17 times normal during chronic sodium depletion. After blockade of the adrenergic nervous system and the renal prostaglandins, PRA was 10 times normal during the acute phase of one-kidney renovascular hypertension. These findings demonstrate that other important mechanisms, possibly both the renal vascular receptor (so-called baroreceptor) and the macula densa, were involved. Both PGI2 and PGD2 given intrarenally increased renin release in both filtering and nonfiltering kidneys, but PGI2 was more potent than PGD2. Available evidence favors a role of PGI2 and it seems likely that the site of action is on the JG cells. Indomethacin produced a profound drop in CCr and CPAH during sodium depletion and in experimental heart failure which demonstrates an important role for the renal prostaglandins in the control of renal arteriolar tone. An important incidental finding is that renal denervation combined with propranolol administration decreased PRA from very high levels to normal in 50% of the dogs with experimental low output heart failure and a concurrent striking natriuresis occurred.

Animals↗