Antihypertensive therapy with triamterene-hydrochlorothiazide vs amiloride-hydrochlorothiazide. Comparison of effects on urinary prostaglandin E2 excretion.

Amiloride hydrochloride has now been recognized as a safe and effective potassium-sparing diuretic alternative to triamterene with a similar mechanism of pharmacologic activity. Studies were undertaken to assess the difference between therapy with the triamterene-hydrochlorothiazide combination (Dyazide) and an amiloride hydrochloride-hydrochlorothiazide combination (Moduretic) on renal prostaglandin production, since an increase in renal prostaglandin synthesis has been shown to mediate or enhance the pharmacologic action of certain diuretic drugs. Eight subjects treated for four weeks with triamterene-hydrochlorothiazide were compared with nine patients similarly treated with amiloride-hydrochlorothiazide. A 24-hour urine sample for prostaglandin E2 (PGE2) assay was collected under control conditions and after six weeks of therapy with either diuretic in all patients. The PGE2 excretion increased in the amiloride-hydrochlorothiazide-treated group; in the other group PGE2 excretion actually declined. It is concluded from these studies that therapy with amiloride-hydrochlorothiazide enhanced renal PGE2 production, whereas that with triamterene-hydrochlorothiazide actually decreased renal PGE2 production. This difference is an important renal consequence of the use of either drug and should be considered in the choice between these diuretic combinations.

Serum calcium in blood pressure regulation during hemodialysis.

Frequent hypotensive episodes developed in a 56-year-old man, who was receiving long-term hemodialysis therapy, at the time he had a uremic pericardial effusion. During dialysis with an inadvertent calcium infusion, however, the mean blood pressure (BP) was sustained and even rose from 93 to 133 mm Hg. During continued dialysis to restore the serum calcium level from a peak of 17.4 to 12.0 mg/dL, mean arterial pressure decreased back to 93 mm Hg. In contrast, BP had fallen in three of six preceding dialysis treatments and five of nine subsequent dialysis treatments, all at the same ultrafiltration rate. This report suggests the importance of serum calcium to BP regulation during hemodialysis.

Hemoglobin A1 in renal transplant recipients.

Studies were undertaken to determine levels of hemoglobin A1 in renal and heart transplant recipients. Hemoglobin A1 was measured by separation from Hb A using an affinity-column chromatography system. Significantly elevated levels of Hb A1 were found in all renal transplant patients; diabetic transplant recipients had the highest levels. There was no correlation between serum creatinine and Hb A1 levels in these transplant recipients. The Hb A1 level did correlate with the prior level of glycemia in these patients. Our findings raised the specter of the consequences of disturbed carbohydrate metabolism in these patients as not being different than that observed with other forms of end-stage renal disease management. Finally, in both diabetic and nondiabetic renal transplant recipients, measurement of Hb A1 can serve as a useful adjunct to assess prior glycemia when such information is not available to the clinician.

Saralasin acetate test in renal transplant hypertension. Report of 17 cases and a review of the literature.

The saralasin acetate test was performed in 17 hypertensive patients with renal transplants. These results were compared with 39 previously published reports of transplant patients who had been tested in the same manner. Eighty-two percent of our patients had a positive saralasin acetate test, suggesting renin-dependent hypertension. Baseline plasma renin activity (PRA) was significantly higher in patients with positive tests (6.96 +/- 1.75 v 2.88 +/- 0.53 ng/mL/hr). However, positive tests were obtained in several patients who had normoreninemia, and PRA levels did not correlate with the magnitude of vasodepressor BP response to saralasin. Transplant artery stenosis, acute rejection, and chronic rejection were the most common posttransplant complications associated with a positive test, but several patients had hypertension alone. While highly sensitive for renin-dependent hypertension posttransplantation, the test had poor specificity for identification of any one cause of posttransplant hypertension.

Effect of clonidine therapy on renal hemodynamics in renal transplant hypertension.

Antihypertensive medications have a variable effect on renal hemodynamics and may contribute to renal insufficiency in some patients. Since clonidine has actually been found to improve renal hemodynamics in patients with essential hypertension, we studied the effects of clonidine therapy in patients with renal transplant hypertension. Baseline measurements of BP and renal hemodynamics were made in six patients after two weeks of therapy with furosemide. Clonidine was then added and titrated until BP was controlled. Repeated measurements of renal hemodynamics were made four and 16 weeks after clonidine therapy was begun. Glomerular filtration and effective renal plasma flow as assessed by inulin and aminohippurate sodium clearances were preserved during prolonged clonidine therapy.

Hypertension associated with hyperparathyroidism is not responsive to angiotensin blockade.

Patients with primary hyperparathyroidism are frequently hypertensive. Studies were performed to determine whether the hypertension in this disorder could be corrected by saralasin infusion. Five patients with primary hyperparathyroidism and one patient with secondary hyperparathyroidism were salt depleted before saralasin testing by the administration of 1 mg/kg furosemide at 1700 h on the evening before testing. Blood pressure was measured every 2 min by an automatic recording device. Saralasin was given as a continuous iv infusion of 1, 3, 6, and 10 micrograms/kg . min for 30 min. Blood for measurement of PRA was drawn 4 min before, immediately before, and 4, 8, 12, 16, 22, 30, 60, and 90 min after the infusion was begun. Saralasin did not reduce blood pressure in these patients. The mean postsaralasin blood pressure (12--20 min after the start of the infusion) was 155/102 mm Hg compared to the control blood pressure of 156/101 mm Hg (blood pressure at -4 and 0 min). The inability of saralasin to effect a vasodepressor response was unexpected, since the mean PRA before saralasin infusion was elevated at 1895 ng/dl . 3 h (normal range, 409--818 ng/dl . 3 hr; 95% confidence limits). These studies suggest that the hypertension associated with hyperparathyroidism is not renin dependent.

Systemic and renal vascular responses to dietary calcium and vitamin D.

To assess the consequences of hypercalcemia on systemic and renal hemodynamics, vasoactive hormones, and water and electrolyte excretion in intact, conscious mongrel dogs, measurements in 10 dogs receiving 100 mg/kg calcium gluconate and 10,000 U/kg vitamin D daily for 2 weeks were compared with measurements made in 10 time-control dogs not receiving calcium or vitamin D. Hypercalcemia induced by dietary supplementation with calcium and vitamin D resulted in profoundly reduced glomerular filtration rate (40 vs 78 ml/min in controls; p less than 0.005), estimated renal plasma flow (145 vs 267 ml/min in controls; p less than 0.005), and renal blood flow (254 vs 441 ml/min in controls; p less than 0.005). Renal resistance was significantly increased in the hypercalcemic dogs (0.57 +/- 0.07 vs 0.28 +/- 0.01 mm Hg/ml/min; p less than 0.005). Hypercalcemia also resulted in increased fractional excretion of water (4.8 vs 1.4% in controls; p less than 0.005), sodium (1.4 vs 0.6% in controls; p less than 0.005), calcium (1.7 vs 0.7% in controls; p less than 0.01), and magnesium (10.2 vs 4.1% in controls; p less than 0.005). Systolic blood pressure (160 vs 172 mm Hg in controls; p less than 0.05) and stroke volume were lower (0.024 vs 0.036 L/beat in controls; p less than 0.005) in hypercalcemic dogs, presumably because of the diuresis, while total peripheral resistance was higher (36 vs 31 mm Hg/L/min; p less than 0.05) in controls. Magnesium levels were significantly lower in the experimental group (1.3 vs 1.7 mg/dl in controls; p less than 0.0005). Aldosterone levels, plasma renin activity, and urinary prostaglandin excretion were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt sensitivity in blacks. Salt intake and natriuretic substances.

Accumulating evidence suggests that hypertension in blacks is manifested in part by impaired renal excretion of salt. Consequently, this study was performed to determine if hypertensive and normotensive black subjects differ in their ability to generate known natriuretic substances. Fourteen normotensive and 11 hypertensive blacks were maintained on constant metabolic diets containing either 40 or 180 mmol of salt per day for 14 days each. During the last 4 days of each salt intake period, urine was collected for measurement of sodium, dopamine, and norepinephrine. On the last day of each 14-day dietary period, blood pressures were measured, blood was collected for measurement of plasma atrial natriuretic factor (ANF) and aldosterone, and urine was collected over 2 hours for measurement of prostaglandin E2 (PGE2). Both the normotensive and the hypertensive groups manifested salt sensitivity; their mean arterial pressure rose by 7 +/- 0.2 and 6 +/- 0.2%, respectively, when salt intake was increased from 40 to 180 mmol/day. The hypertensive group exhibited decreased (p less than 0.05) dopamine excretion as compared with the normotensive group for both dietary salt intakes. Plasma ANF levels increased (p less than 0.05) in the hypertensive group, but not in the normotensive group, with increasing dietary salt. Plasma aldosterone and urinary norepinephrine and PGE2 were comparable in the two groups for both dietary salt intakes. These data suggest that salt sensitivity is not unique to hypertensive blacks but occurs in normotensive blacks as well. Decreased renal production of dopamine may be a pathogenic factor in the development and maintenance of hypertension in blacks.

Blood pressure lowering and potassium conservation by triamterene-hydrochlorothiazide and amiloride-hydrochlorothiazide in hypertension.

Effects of once-daily doses of 50 mg triamterene with 25 mg hydrochlorothiazide and 5 mg amiloride with 50 mg hydrochlorothiazide were compared in a randomized, multicenter study of 84 adult subjects with mild to moderate hypertension (diastolic blood pressure 90 to 114 mm Hg). After a 3-wk placebo lead-in period, the subjects entered a 6-wk treatment period. The two drug regimens were compared with respect to antihypertensive effects and effects on serum potassium and magnesium levels during the final week of drug therapy, with the use of the last week of placebo therapy as a covariate. Both drug regimens substantially reduced mean supine systolic and diastolic blood pressures to well within normal limits; there was no significant difference the two groups. Twenty-four of the 41 subjects receiving triamterene-hydrochlorothiazide (59%) and 29 of the 43 patients receiving amiloride-hydrochlorothiazide (67%) had diastolic blood pressure less than 90 mm Hg at week 9. Five subjects receiving amiloride-hydrochlorothiazide (12%) and two subjects receiving triamterene-hydrochlorothiazide (5%) had hypokalemia (serum potassium level less than 3.5 mEq/l) at week 9. The average decrease in serum potassium levels during amiloride-hydrochlorothiazide therapy (-0.33 +/- 0.08 mEq/l) was greater than that after triamterene-hydrochlorothiazide (- 0.08 +/- 0.07 mEq/l). Serum magnesium levels were not changed by either regimen. Weight loss was greater in the amiloride-hydrochlorothiazide group than in the triamterene-hydrochlorothiazide group.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic considerations in the approach to diabetic hypertensive patients.

The effects of antihypertensive drugs on glucose metabolism are an important consideration in the selection of pharmacologic therapy for diabetic patients. Diuretics can elevate blood glucose levels, aggravate glucose intolerance, and predispose diabetic patients to hyperosmolar non-ketotic coma. Beta-blocking drugs often exacerbate and prolong insulin-induced hypoglycemia in diabetics. Beta-blockers may also cause hyperglycemia. Central agonists, alpha-blockers, and vasodilators apparently have neutral effects on carbohydrate metabolism in normal subjects or in hypertensive diabetics. Calcium channel blockers may disturb carbohydrate metabolism in diabetic patients. Angiotensin-converting enzyme inhibitors have little effect on glucose metabolism. Because diabetic patients are prone to fluid, electrolyte, hormone, and lipid disturbances, it is important to consider the effects of antihypertensive drugs on these aspects of metabolism when selecting pharmacologic therapy. The effects of various antihypertensive drugs on sodium, calcium, magnesium, and acid/base balance are reviewed. The effects of these drugs on serum uric acid and potassium, as well as on hormone and lipid levels, are also considered.

Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.

The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.

Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension.

The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.

Efficacy and safety of two-year therapy with transdermal clonidine for essential hypertension.

We evaluated the safety and efficacy of transdermal clonidine (TC) in 23 patients with essential hypertension over a two-year period. Fourteen patients achieved control of blood pressure using TC alone. Six patients achieved control with a combination of TC and the diuretic chlorthalidone (CH). Three patients had control with CH alone or did not achieve control with either TC alone or TC plus CH and were dropped from the study. Of the 20 patients remaining in the study, six patients remained on TC or TC plus CH for the two-year study. Ten of the 20 patients quit the study because of skin reactions and four because of other side effects. No clinically significant changes were noted in serum or urinary laboratory parameters. Finally, TC was effective as long-term monotherapy for essential hypertension in only four of our patients. The major limitation is skin-related side effects.

High-calcium diet in spontaneously hypertensive rats: intervention with calcium antagonist verapamil.

A number of studies have shown an antihypertensive effect for high-calcium diets, but others have found no effect or, even a prohypertensive effect. Because of these disparate results, studies were conducted in spontaneously hypertensive rats (SHR) fed either a normal calcium diet (1.0% calcium) or a high-calcium diet (4.0% calcium) with or without verapamil HCl (50 mg/kg body weight) from ages 5 to 12 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured by indirect tail cuff method. During the analysis of the electrolytes and vasoactive hormones monitored in this study, it was found that rats fed high-calcium diet had significantly elevated serum ionized and total calcium and calcium excretion. Systolic blood pressure for the verapamil-normal calcium diet (week 5, 148 +/- 4 mm Hg; week 7, 162 +/- 4 mm Hg) did not differ significantly from that of normal calcium diet (week 5, 152 +/- 2 mm Hg; week 7, 160 +/- 1 mm Hg). The high-calcium diet potentiated the development of hypertension, i.e., SBP was (157 +/- 2 mm Hg) on the 5th week and (174 +/- 4 mm Hg) on the 7th week. Conversely, verapamil high-calcium diet prevented the development of hypertension (week 5, SBP was 139 +/- 4 mm Hg; week 7, SBP was 146 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal hemodynamic effects of chronic ketorolac tromethamine treatment in aged lean and obese Zucker rats.

Ketorolac tromethamine is a relatively new non-steroidal anti-inflammatory drug (NSAID), with potent analgesic activity. Similar to other NSAIDs, ketorolac has the potential to impair renal function. To assess the renal hemodynamic impact of the ketorolac in aged lean and obese rats, ketorolac was orally administered to 46-week-old lean and obese Zucker rats for two weeks. Ketorolac was mixed with rat chow in a manner to provide a dose equivalent to 15 mg/kg body weight/day. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured under anesthesia by standard inulin and p-aminohippuric acid clearance method, respectively. Urinary prostaglandin (PG) E2 excretion was measured before and after ketorolac treatment. Ketorolac treatment significantly reduced obese rat GFR (0.47 +/- 0.08 vs 0.78 +/- 0.03 ml/min/g, p < 0.002) and ERPF (1.12 +/- 0.14 vs 2.36 +/- 0.26 ml/min/g, p < 0.001) relative to obese control rats. In comparison, ketorolac did not significantly alter lean rats GFR (0.77 +/- 0.04 vs 0.91 +/- 0.06 ml/min/g) or ERPF (1.92 +/- 0.20 vs 2.48 +/- 0.15 ml/min/g) relative to lean control rats. Chronic ketorolac treatment significantly reduced hematocrit by 20 and 30 percent in lean and obese rats relative to controls, respectively. The renal vascular resistance was significantly increased with ketorolac treatment in obese rats (36 +/- 4 vs 79 +/- 14 mmHg/ml/min, p < 0.001) but not lean rats (28 +/- 3 vs 38 +/- 5 mmHg/ml/min, NS) relative to corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal hemodynamic and histological consequences of diets high in unsaturated fat, protein or sucrose in obese Zucker rats.

The objective of this study was to determine the long-term effect of different dietary macronutrients on renal hemodynamics in obese Zucker rats. Female obese (fa/fa) Zucker rats were allowed to eat control chow (ObCL) or diets high in unsaturated fat (ObHF), protein (ObHP) or sucrose (ObHS) for a period of 24 weeks. Lean chow fed (LnCL) Zucker rats served as lean controls. After 24 weeks of dietary treatments, glomerular filtration rate (GFR, ml/mg/g, mean +/- SE) of ObHP and ObHS (0.38 +/- 0.06 and 0.27 +/- 0.05) rats were significantly (p < 0.005) lower than ObCL (0.74 +/- 0.05) and ObHF (0.88 +/- 0.1) rats. In a similar manner, the effective renal plasma flow (ERPF, ml/min/g) was significantly (p < 0.005) lower in ObHP and ObHS (1.28 +/- 0.16 and 1.04 +/- 0.2) than ObCL (2.46 +/- 0.31) or ObHF (2.85 +/- 0.25) rats. The ObHF rats appeared "protected" since they had similr GFR and ERPF but less proteinuria and glucosuria than ObCL rats. Histological examination of renal tissue from ObHP and ObHS fed rats revealed significant (p < 0.005) increase in sclerosis relative to ObCL rats. The sclerosis of renal tissue in ObHF was minimized and was found to be similar to ObCL rats. The mean arterial pressure and heart rates were similar in all dietary treated obese Zucker rats. When comparing obese and lean controls, ObCL rats had significantly (p < 0.03) lower GFR (0.74 +/- 0.05 vs 0.92 +/- 0.05) but similar ERPF (2.46 +/- 0.3 vs 2.82 +/- 0.12) than LnCL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypercalcemic hypertension in hemodialysis.

Hypertension refractory to standard dialystic maneuvers developed in a 25-year old female who had been on long-term hemodialysis. Lowering the target dry weight and adding antihypertensives did not ameliorate the hypertension. Hypercalcemia, due to vitamin D administration, was discovered and, following its correction, there was subsequent normalization of the blood pressure. This report discusses some of the mechanisms whereby calcium can interface with blood pressure regulatory mechanisms in individuals with end stage renal disease.

Chronic interstitial nephritis. Its occurrence with oxalosis and anti-tubular basement membrane antibodies after jejunoileal bypass.

A 38-year-old woman suffered rapid onset of renal failure between 11 and 15 months after undergoing a jejunoileal bypass for morbid obesity. Microscopic examination of renal biopsy specimens revealed oxalosis and severe tubulointerstitial nephritis. Immunofluorescence microscopy disclosed linear staining of tubular basement membranes with antisera to IgG and C3, which suggests antitubular basement membrane disease, a side effect not previously recognized with jejunoileal bypass. Possible mechanisms leading to the formation of these antibodies include (1) oxalate damage to renal tubules with release of tubular basement membrane antigens, and (2) bacterial overgrowth in the bypass segment, with mucosal damage and release of intestinal mucosal antigens that share antigenetic determinants with renal proximal tubules. Anti-tubular basement membrane disease may be an additional mechanism that produces or enhances renal damage in patients with jejunoileal bypass.

Non-renin dependent hypertension in renal allograft rejections. A structural and functional analysis.

A 25-year-old recipient of a cadaveric renal allograft underwent three acute rejection episodes within the first 40 days after transplant, the final episode necessitating nephrectomy. The saralasin acetate infusion test and plasma renin activity (as measured by radioimmunoassay of angiotensin I) were used as functional tests of the renin-angiotensin axis. Biopsy specimens of the allograft one hour after implantation and sections of the nephrectomy specimen were fixed and stained with hematoxylin-eosin for structural analysis. On three separate dates, during the final rejection episode, saralasin acetate infusion of up to 20 micrograms/kg/min failed to lower BP significantly. The final two trials were preceded by furosemide administration the previous day to reduce fluid volume. Plasma renin activity was low on all three dates. On nephrectomy, the allograft was noted grossly to be infarcted. Histologic examination revealed cortical necrosis, markedly narrowed or occluded intrarenal vessels, and extremely narrowed large vessels within the renal pelvis. The allograft renal artery was thickened and narrowed. From our structural and functional analysis we conclude that (1) hypertension, in this case, was probably volume dependent and was clearly renin independent; and (2) the low renin levels are explainable on the basis of extensive vascular occlusion producing renal infarction and resulting in a kidney incapable of producing significant amounts of renin (autonephrectomy).

The effects of changes in serum calcium and parathormone on plasma renin activity in intact mongrel dogs.

Studies were undertaken to extend previous observations of the interaction between calcium and parathormone on renin synthesis by the kidney. Intact normovolemic mongrel dogs between 15 and 25 kg were used for all studies. Plasma renin activity (PRA) was measured by radioimmunoassay. Hypocalcemia produced by thyroparathyroidectomy or chelation with EDTA resulted in an elevated PRA of 3.76 +/- .86 ng/ml/hr in 17 dogs compared to 1.5 +/- .29 ng/ml/hr in 14 controls (p less than .05). In 5 renovascular dogs calcium-channel blockade with nifedipine resulted in a higher PRA of 31.8 +/- 0.5 compared to 11.9 +/- 1.1 ng/ml/hr in 23 renovascular controls, p less than .001. The reactive hyperreninemia following angiotensin blockade was greater in 22 hypocalcemic (10.94 +/- 2.03 ng/ml/hr) dogs compared to 14 controls (1.32 +/- .34 ng/ml/hr), p less than .001. Results with calcium antagonism on PRA levels in renovascular dogs were found similar to those described with angiotensin blockade. We conclude from these studies that calcium-channel blockade or calcium reduction independent of a rise in parathormone was associated with an elevation of PRA in normal and renovascular hypertensive dogs. The rise in PRA could occur without changes in blood pressure or volume, consistent with an interruption of the short feedback loop control of renin synthesis by calcium antagonism. Finally, hypocalcemia and calcium-channel blockade resulted in reactive hyperreninemia greater than or equal to that seen after angiotensin blockade in both groups of dogs, again suggesting interference with the short feedback loop control of renin synthesis.