Plasma renin activity (PRA) was measured during the administration of clonidine (0.1 mg twice daily) to 11 patients with essential hypertension. After eigth weeks a trend toward an increase in PRA was noted. This increase was significant in "low renin" subjects (less than 1 ng Al/ml/hr, n = 7) in whom PRA (ng/ml/hr +/- SEM) rose from a control value of 0.7 +/- 0.1 to 2.0 +/- 1.1 at one week, 5.6 +/- 2.1 at four weeks, and 4.4 +/- 1.0 at eight weeks (p less than 0.05). In contrast, in a small group of "normal renin" patients (n = 4), PRA did not change significantly but tended to decrease on clonidine therapy from 9.2 +/- 3.4 at control to 3.3 +/- 2.0 at one week, 3.4 +/- 0.6 at four weeks, and 4.7 +/- 1.7 ng Al/ml/hr at eight weeks. Plasma renin substrate and serum and urinary electrolytes did not change significantly in either group and blood pressure reduction was comparable in the two groups. A strong negative correlation (r = -0.84, p less than 0.001) was found between changes in creatinine clearance and changes in PRA. Previous studies have implicated alpha-adrenergic receptors as the site of clonidine actions on blood pressure and renin release. The observed renin stimulation during chronic administration of clonidine to "low renin" patients with essential hypertension may imply an altered intrarenal alpha-receptor function in "low renin" essential hypertension.

Adult↗

PubMedDate not supplied

Studies on renin activation in normal human plasma.

The phenomenon of plasma renin activattion by acid dialysis and preincubation with trypsin was studied in normal human plasma. Activation of plasma renin by exposure to pH 3.3 was shown to require at least one dialysis step and could be inhibited by the presence of Trasylol, indicating the involvement of a protease in acid activation. Amniotic fluid exposed to pH 1.5 to destroy renin and renin substrate was also found to contain an enzyme capable of activating plasma renin. The Michaelis-Menten constant Km and the molecular weight of activated "renin" were found to be similar to those of normal plasma renin. Inactive renins or renin-like enzymes were partially purified from plasma by affinity chromatography on concanavalin A, precipitation with (NH4)2SO4 and isoelectric focusing. Trypsin and acid exposure gave similar results with regard to the activation of this zymogen, suggesting that trypsin and acid dialysis may increase plasma renin activity by the same mechanism.

Amniotic Fluid↗

PubMedDate not supplied

Studies on angiotensinogen of plasma and cerebrospinal fluid in normal and hypertensive human subjects.

The presence of a renin-angiotensin system in the central nervous system (CNS) has been demonstrated by several investigators, but little is known regarding the origin of its components. In this study we have compared the immunological and physical-chemical nature of angiotensinogen in plasma and cerebrospinal fluid (CSF) of human subjects and explored whether differences are present in CSF angiotensinogen concentrations of normal and hypertensive subjects. No significant differences in the nature of plasma and CSF angiotensinogen was observed with respect to molecular weight (65-70,000) electrophoretic mobility (RFalb = 0.67 plus or minus 0.003) or angiotensin I (AI) generated (pI = 6.6). Following isoelectric focusing, the plasma angiotensinogen was shown to consist of a single component with an isoionic point of 4.40 plus or minus 0.04. CSF angiotensinogen, on the other hand, resolved into three components (pI = 4.76 plus or minus 0.02; 5.16 plus or minus 0.04; 5.76 plus or minus 0.04). Although no correlations were observed between angiotensinogen levels in the CSF or plasma with blood pressure (BP), a statistically significant difference in angiotensinogen concentration of both plasma and CSF was observed between normotensive and hypertensive subjects. The differences in the chemical and immunological nature of human plasma and CSF angiotensinogens suggest that the angiotensinogen of CSF is not of peripheral origin.

Adult↗

PubMedDate not supplied

In vivo and in vitro alterations of active and inactive plasma renins in the rat.

The levels of active, inactive, and total renin (trypsin treatment) were measured in rat plasma before and after in vivo stimulation or suppression of active plasma renin. Stimulation of active renin was accompanied by either an increase (low sodium diet), no change (pentobarbital anesthesia plus hemorrhage), or fall (pentobarbital anesthesia) in the plasma levels of inactive renin, while suppression of active renin was accompanied by a fall (high sodium diet) or mild but nonsignificant increases (clonidine or saline infusion) of the inactive enzyme. These results suggest the possible independence of in vivo regulation of active and inactive renin in the rat. Trypsin activation of plasma fractions obtained by isoeletric focusing indicated a minimum of three activable forms of inactive renin (pH 4.4, 4.6, 4.8). Inactive enzymes could not be completely separated from active renins by this technique. Isoelectric focusing indicated a similar lowering of the isoelectric points of the five detectable active renins of rat plasma following in vivo stimulation of the renin system (ether anesthesia plus hemorrhage) or trypsin treatment of normal rat plasma before fractionation. These results indicate that similar renins are activated both in vivo and in vitro. Although trypsin is not the physiological activator of renin, a similar enzymatic cleavage resulting in activation appears to occur in vivo.

Animals↗