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K E Lentz

Publications and source records attributed to K E Lentz.

12 recordsLinked to original sources
PubMed1978

A comparison of the substrate specificities of cathepsin D and pseudorenin.

Cathepsin D, purified from hog spleen, releases angiotensin I from tetradecapeptide renin substrate and from protein renin substrates purified from hog and human plasma. However, the enzyme does not act on the naturally occurring renin substrate as it exists in plasma nor on purified substrate in the presence of plasma. Cathepsin D releases angiotensin I quantitatively from tetradecapeptide renin substrate and does not further degrade the angiotensin I on prolonged incubation. The pH optimum for cathepsin D prolonged incubation. The pH optimum for cathepsin D acting on tetradecapeptide renin substrate is 4.5, and there is very low activity above pH 7. These properties are very similar to those of pseudorenin, an angiotensin-forming enzyme originally isolated from human kidney, indicating that cathepsin D and pseudorenin may be identical.

Animals↗
PubMed1978

Multiple forms of renin substrate in human plasma.

Renin substrate (angiotensinogen) in unfractionated human plasma has been shown to exist in multiple forms by DEAE-cellulose chromatography and isoelectric focusing. Two major and 5 to 6 minor peaks were resolved by using a descending pH gradient elution from DEAE-cellulose columns. The two predominant forms were eluted at or near pH 4.8 and 4.4 and usually accounted for 40--50% of the recovered substrate activity. The elution pH values of the various forms were nearly constant among plasmas from normal males and females and in diabetes, early and late pregnancy and estrogen substitution therapy. The relative distribution of components was not affected by prior freezing of the plasma or by dialysis against the column buffer. Eight renin substrate forms were clearly resolved during isoelectric focusing of plasma from a woman on estrogen substitution therapy. Four of these focused at pH 4.79, 4.88, 4.94 and 5.02 in 1% (w/v) ampholytes pH 3.5--5 and were nearly equal in substrate amount. Together these 4 forms constituted 66% of the total recovered activity. A similar pattern but with decreased amounts of each form of substrate was obtained with normal plasma.

Angiotensinogen↗
PubMed1977

Chronic one-kidney hypertension in rabbits. III. Renopressin, a new hypertensive substance.

The blood pressure of rabbits with chronic one-kidney hypertension can be lowered to normal by immunization with hog kidney cortex preparations that do not contain renin, thus providing evidence for a new factor essential for the maintenance of an elevated blood pressure. A search for the new factor has led to the discovery of a hypertensive substance which we have named renopressin. Subcutaneous injection of the new substance into normal rabbits produces a delayed, slow increase in blood pressure, and after a few days the development of a moderate hypertension which persists indefinitely. The response of the blood pressure to renopressin is totally unlike that to renin. While the pressor action of renin can be blocked by an angiotensin II antagonist, the hypertension caused by renopressin cannot. Renin can increase the blood pressure of hypertensive rabbits; renopressin has no effect. The blood pressure of hypertensive rabbits and of normal rabbits made hypertensive by injection of renopressin can be lowered to normal by passive immunization with the same antibody preparation. The evidence is consistent with the possibility that renopressin and the agent causing the elevation of blood pressure in hypertensive rabbits are similar or identical.

Angiotensin II↗
PubMed1977

New developments in our knowledge of the chemistry of renin.

Although the role of renin in hypertension continues to be incompletely defined, recent progress in the chemistry of renin has been considerable. Extensive purifications of hog kidney renin and the renin-like mouse submaxillary gland enzyme have been achieved. Various inhibitory peptides based on tetradecapeptide renin substrate have been useful in renin kinetic studies and in renin affinity chromatography. Classification of renin as an acid protease results from its marked inhibition by pepstatin and from the discovery that free carboxyl at the active site is essential for activity in human and hog kidney and mouse submaxillary gland enzymes. The presence of pseudorenin in all tissues has limited the use of model peptides as renin substrates in plasma and crude tissue extracts, since the proteolytic properties of the two enzymes are nearly identical. The existence of renin in multiple, chromatographically separable forms has been known. More recently inactive forms have been found in plasma, amniotic fluid, and hog and rabbit kidneys. Prolonged storage or treatment with acid, trypsin, or pepsin causes activation; in some instances the conversion is from a higher than normal molecular weight. The implications of these findings with respect to the renin-angiotensin system need much further investigation.

Amino Acid Sequence↗
PubMed1976

The biochemistry of the renin-angiotensin system and its role in hypertension.

The renin-angiotensin system has an important role in maintaining elevated blood pressure levels in certain forms of experimental and human hypertension. Renin, an enzyme produced by the juxtaglomerular cells of the kidney, acts on a protein substrate found in the alpha 2-globulin fraction of the plasma to produce a decapeptide, angiotensin I. This decapeptide is not directly pressor, but on passage through the pulmonary circulation is converted to an octapeptide, angiotensin II, a very potent pressor substance which acts by causing constriction of arteriolar smooth muscle. In addition to its direct action which increases blood pressure, angiotensin II acts on the adrenal cortex to cause the release of the sodium-retaining hormone aldosterone. Recent evidence suggests that this action may be mediated by the heptapeptide, angiotensin III. Both renin and its protein substrate exist in multiple forms and renin may also exist as a high molecular-weight "pro-hormone," although the physiologic significance of these forms is not clear. The elucidation of the biochemistry of the renin-angiotensin system has provided us with inhibitors which allow the system to be blocked effectively in vivo. Thus, angiotensin antagonists such as Sar 1, IIe 8-angiotensin II and converting enzyme inhibitors such as BPP 9a (SQ 20881) have proved useful in the study of experimental and human hypertension.

Aldosterone↗
PubMed1976

Kinetic properties of pulmonary angiotensin-converting enzyme. Hydrolysis of hippurylglycylglycine.

Some of the kinetic properties of angiotensin-converting enzyme (peptidyl-dipeptide hydrolase, EC 3.4.15.1) purified from hog lung have been determined using hippurylglycylglycine as substrate. The effects of pH and ionic environment on enzyme activity are complex and interdependent. At 0.1 M NaCl, the pH-activity curve shows an abrupt decrease in V/Km as the pH rises from 6 to 6.5, implying that ionization of a group in the enzyme with a pK in this range aids in binding of the substrate. Chloride is required for enzyme activity; there are two phases in the effect of NaCl. At both pH 6 AND 8, THE FIRST PHASE (UP TO 0.1 M NaCl) is activation. The second phase (above 0.1 M) at pH 6 is inhibition, while at pH 8 there is further activation which appears to be dependent upon ionic strength rather than a specific Cl-effect. Activation by cobalt and inhibition by EDTA are somewhat more effective at pH 6 than at pH 8. The nonapeptide inhibitor less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro is nearly equipotent at both pH 6 and 8, but Arg-Pro-Pro is more inhibitory at pH 8 than at pH 6.

Animals↗
PubMed1976

Partial purification of a high molecular weight renin from hog kidney.

Previous investigators have reported finding a high molecular weight (HMW) renin in various species which is activated by acidification. Two laboratories have reported that a decrease in molecular weight of the renin accompanies the acidification step. This report describes the partial purification of an HMW renin from hog kidney extracts which had previously been acidified to pH 2.5. The HMW renin, with a molecular weight of 57,000-59,000, constitutes only a small, relatively constant fraction of the total renin isolated. Omission of the acidification step or initial acidification to pH 1.6 does not change the amount of HMW renin significantly. The HMW renin attacks the protein substrate to produce angiotensin at about one-fourth the rate expected, based upon the rate at which it cleaves the tetradecapeptide substrate or a model nonapeptide substrate. It is inactivated by antiserum to hog kidney renin prepared in dogs. It is less stable than hog renin when stored at 0 degrees C. The HMW renin has a pH optimum between 6.5 and 7.0. It is not activated by acidification to pH 3, nor by tryptic or peptic digestion. We have been unable to activate HMW renin or to change its molecular weight by procedures reported by other investigators and therefore conclude that the HMW renin differs from material previously reported and may be an isoenzyme of renin.

Angiotensin II↗
PubMed1976

Chronic one-kidney hypertension in rabbits. II. Evidence for a new factor.

The arterial pressure of rabbits with chronic one-kidney hypertension can be lowered to normotensive levels by direct immunization with preparations made from the cortex of hog kidneys. Hypertensive rabbits that are immunized with large amounts of renin may develop high plasma antirenin titers without affecting their blood pressure. Removal of renin by chromatography on columns of immobilized antirenin yields preparations with little or no renin. Such preparations may be effective in lowering blood pressure although they do not elicit the formation of plasma antirenin and the rabbits remain sensitive to challenging doses of rabbit renin. The evidence suggests that an unknown substance is responsible for the development of a cross-reacting antibody that neutralizes an unknown factor that is essential for the maintence of an elevated blood pressure level in rabbits with chronic one-kidney hypertension.

Animals↗