[The treatment of arterial hypertension. An inquiry among doctors in general practice]. / Die Therapie der arteriellen Hypertonie. Eine Umfrage bei niedergelassenen Arzten.

BACKGROUND AND OBJECTIVE: There are many drugs used in the treatment of hypertension. National and international expert committees regularly publish recommendations for antihypertensive treatment. It is not known how doctors in general practive treat hypertension. METHOD: Questionnaires were sent to 1540 internists, general practitioners and practical doctors in Hamburg, to provide information on their management of hypertensives. There were 458 replies (30%). RESULTS: 38% of replying doctors thought that treatment was required if the blood pressure was above 140/90 mmHg, 53% set the level at 160/95 mmHg and 10% above 180/100 mmHg. Internists among them treated hypertension more vigorously than the general practitioners. The most important qualities of a good antihypertensive drug were effective blood pressure reduction (95%), few side effects (83%) and evidence-based reduction of morbidity and mortality (44%). The most frequently used antihypertensives were ACE inhibitors (98%), followed by beta-blockers (86%), diuretics (60%), calcium antagonists (54%) and AT-1 blockers (22%). The most frequently prescribed calcium antagonist was amlodipine (38%), followed by nifedipine preparations (29%), verapamil (18%) and nitrendipine (6%). Diuretics were named as the best tolerated group of antihypertensive drugs, followed by ACE inhibitors, beta-blockers and AT-1-blockers. ACE inhibitors were preferentially used for patients with diabetes mellitus (84%), heart failure (90%) and renal disease (68). Beta-blockers were prescribe for only 72% of patients with coronary heart disease. 212 of doctors did not prescribed new antihypertensives immediately they became available, while 72 used them at once. CONCLUSION: This survey indicates that internists and general practitioners treat hypertensives according to official recommendations and guidelines. But there is a need for further education regarding the definition of normotensive values, and improvement is still possible in the treatment of associated diseases such as diabetes, coronary heart disease and renal disease.

Effect of renovascular hypertension on experimental glomerulonephritis in rats.

Systemic hypertension is a major risk factor that determines the rate of progression of kidney disease. The underlying mechanisms, however, are incompletely understood. To gain insight into these mechanisms, the present study was undertaken to characterize the effects of renovascular hypertension on the course of anti-thymocyte antibody-induced glomerulonephritis. Glomerulonephritis was induced in rats 6 weeks after the initiation of two-kidney, one-clip hypertension, when blood pressure was already increased. Structure and function of the clipped and the nonclipped kidney were examined 5 days later. Glomerular filtration rate (GFR) was measured by inulin clearance. The induction of nephritis did not alter the blood pressure in either hypertensive rats or normotensive controls. Albuminuria increased slightly in normotensive rats after the induction of nephritis, whereas no significant differences were found between hypertensive rats with or without nephritis. No significant differences were found for the GFR values of normotensive controls and nephritic animals or for values in the clipped kidney with or without nephritis. However, the GFR of the nonclipped kidney was significantly reduced in nephritic animals as compared with all other groups. Morphologic evaluation revealed that hypertensive rats with nephritis exhibited a combination of characteristics of nephritis and hypertensive glomerular injury. Histologic findings of nephritis, such as glomerular binding of rabbit IgG and glomerular proliferation and mesangial matrix expansion, were similar after the induction of nephritis in controls and in the clipped and nonclipped kidneys of hypertensive animals. However, intraglomerular microaneurysms were significantly more often found in the non-clipped kidneys after the induction of nephritis. Hypertension-induced deterioration of glomerular function was not associated with marked morphologic deterioration but rather with a combination of the characteristics of nephritis and hypertensive glomerular injury.

[Diagnostic and therapeutic procedures by doctors for patients in a hypertensive crisis. An inquiry in 56 internal medicine clinics]. / Diagnostisches und therapeutisches Vorgehen von Arzten bei Patienten mit hypertensiver Krise. Eine Umfrage an 56 internistischen Kliniken.

BACKGROUND AND OBJECTIVE: Despite official guidelines on the diagnosis and treatment of hypertensive crisis, the extent to which they are being followed in routine medical practice is unknown. This study was undertaken to discover how hospital doctors were handling cases of hypertensive crisis (HC). MATERIALS AND METHODS: Physicians were requested to participate in a multiple-choice questionnaire study, relating to the diagnosis of HC, any emergency diagnosis and choice of antihypertensive drugs, these questionnaires to be distributed among the medical staff. Ultimately 463 questionnaires (one per doctor) were sent out and 325 were completed (response rate of 70%). RESULTS: The most frequently mentioned blood pressure values characteristics for HC were > 200 systolic and > 120 diastolic. 160/90 was given most often as the therapeutic goal, which most doctors wanted to reach in an HC within 30 to 60 min. The calcium-antagonist nifedipine was the drug of first choice for almost all clinical presentations. Second was intravenously urapidil, an alpha-agonist. Nitroglycerin was named as first choice only for pulmonary oedema or myocardial infarction. In everyone of the stated conditions most doctors were eager to avoid using beta-blockers. As for the drug of first choice in associated myocardial infarction, 111 doctors named nifedipine, 28 wanted to avoid it and 45 considered it contraindicated. CONCLUSION: These data show a marked discrepancy between recommended guidelines and actual practice in the management of hypertensive crisis.

Chronic angiotensin-converting enzyme inhibition may improve sodium excretion in cardiac transplant hypertension.

Cyclosporine-associated hypertension (CAH) may be mediated in part by sodium and volume retention. To investigate this issue, we studied the effects of a calcium antagonist, nitrendipine (NIT, 10-20 mg b.i.d.), and a converting enzyme inhibitor, lisinopril (LIS, 10-20 mg o.d.), on blood pressure (office BP, 24 hr ambulatory BP), excretion of an acute sodium load (200 mmol/2 hr i.v.), glomerular filtration rate (insulin clearance), cumulative dopamine excretion, plasma atrial natriuretic peptide (ANP), and endothelin excretion in 8 patients with CAH after cardiac transplantation in a double-blind, randomized, crossover trial for 6 weeks. Five patients received a diuretic during the trial at a constant dose. Office diastolic BP (DBP) decreased significantly with LIS from 97 +/- 6 to 87 +/- 9 mmHg and with NIT from 96 +/- 7 to 92 +/- 12 mmHg. Ambulatory 24 hr DBP decreased significantly from 96 +/- 7 mmHg to 86 +/- 10 mmHg (LIS) and to 84 +/- 11 mmHg (NIT). Ambulatory DBP during the day was lowered significantly from 98 +/- 11 mmHg to 87 +/- 10 mmHg (LIS) and to 88 +/- 9 mmHg (NIT) and during the night from 95 +/- 9 mmHg to 86 +/- 8 mmHg (LIS) and to 79 +/- 7 mmHg (NIT). Cumulative sodium excretion 6 hr after an acute sodium load increased to 52 +/- 39 mmol (placebo), 96 +/- 44 mmol (LIS, P < 0.05 vs. placebo), and 71 +/- 34 mmol (NIT). Glomerular filtration rate, cumulative dopamine excretion, ANP, and endothelin excretion did not differ between either treatment group. We conclude, that: (1) both drugs were similar in lowering office BP and during the day, but NIT tended to be more effective during the night; and (2) cumulative sodium excretion during LIS was significantly increased compared with placebo. There was a similar trend during NIT also. Therefore, it is possible that chronic angiotensin-converting enzyme inhibition and possibly calcium antagonists might improve the sodium-retaining state in CAH independent of differences in blood pressure, ANP, dopamine, or renal function.

Resetting of 24-h sodium and water balance during 4 days of servo-controlled reduction of renal perfusion pressure.

This study examines whether an increase in renal perfusion pressure (RPP) is necessary to escape endogenously stimulated Na- and water-retaining mechanisms. In seven dogs stimulation was accomplished by a servo-controlled reduction of RPP (rRPP) below the threshold for pressure-dependent renin release for 4 days. Oral intake was standardized. Plasma renin activity (PRA) rose from 2.5 in controls to approximately 5 ng ANG I.ml-1 x h-1 during rRPP days. Plasma aldosterone concentration (PAC) increased by approximately 50% only on day 1 of rRPP but fell at or below control levels thereafter. The PAC-to-PRA ratio decreased during rRPP days. Atrial natriuretic factor (ANF) rose to values three times higher than in controls. Mean systemic blood pressure (MABP) rose from 111 +/- 12 in controls to 142 +/- 14 mmHg on day 4 of rRPP. On day 1 of rRPP 60% of the Na and 24% of the water intake were retained. However, after 2-3 days the input-output balance was restored but on a higher level of total body Na and total body water (new "set point"). Because elevated systemic MABP could not exert direct pressure effects on the kidneys due to servo control of rRPP, there must be other factors, e.g., fall in PAC, increase in ANF, and changes in intrarenal hemodynamics and physical factors that may have contributed to the resetting of input-output balances during rRPP.

Combination treatment of enalapril with nitrendipine in rats with renovascular hypertension.

We have recently shown that treatment with the calcium channel blocker nitrendipine may aggravate albuminuria and glomerular injury in rats with two-kidney, one clip renovascular hypertension if arterial blood pressure is not reduced. To test whether nitrendipine also exerts its adverse renal effects when normotension is achieved, we examined the effect of combined therapy with nitrendipine and the converting enzyme inhibitor enalapril on blood pressure, albuminuria, glomerular filtration rate, and morphology of the nonclipped kidney. Rats treated with enalapril alone or in combination with the diuretic hydrochlorothiazide or rats treated with nitrendipine alone served as controls. Therapy was started 6 weeks after clipping of one renal artery. Nitrendipine alone did not reduce blood pressure but significantly increased albuminuria, diuresis, glomerular filtration rate, and glomerular volume and injury compared with untreated hypertensive controls. Increase of glomerular filtration rate, diuresis, and albuminuria was reversible after withdrawal of nitrendipine. Treatment with enalapril alone decreased blood pressure significantly but not to normotensive levels and was without significant effect on albuminuria and glomerular morphology. The combination of nitrendipine and enalapril reduced blood pressure to normotensive levels and not only prevented the increase of glomerular volume, glomerular filtration rate, diuresis, and albuminuria caused by nitrendipine alone but furthermore improved glomerular injury and albuminuria to levels not significantly different from normotensive controls. Enalapril in combination with the diuretic had similar beneficial effects on blood pressure, albuminuria, and glomerular injury. These data demonstrate that the adverse effects of nitrendipine monotherapy on glomerular structure and function can be prevented by the combination of nitrendipine and enalapril when blood pressure is normalized.

Effects of nitrendipine and lisinopril on blood pressure and sodium excretion in ciclosporin-associated hypertension after heart transplantation.

Hypertension associated with ciclosporin A may be mediated by sodium and volume retention. Therefore, the effects of an antihypertensive therapy (6 weeks) with nitrendipine (10-20 mg twice daily) or lisinopril (10-20 mg once daily) on office blood pressure, 24-hour ambulatory blood pressure, and left ventricular function were evaluated in a randomised, double-blind cross-over trial in patients after heart transplantation. Nitrendipine and lisinopril were equally effective in lowering office and ambulatory systolic and diastolic blood pressures. After an acute sodium load (210 mval/2 h i.v.), sodium excretion was significantly increased during therapy with lisinopril but only slightly during nitrendipine, indicating that angiotensin-converting enzyme inhibition may improve the sodium-retaining state of heart transplant recipients associated with ciclosporin A.

Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.

The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

[Somatomedin C level and stimulation of growth hormone and adrenal cortex function by administration of releasing hormones and physical exertion in patients with obesity]. / Somatomedin-C-Spiegel und Stimulation von Wachstumshormon und Nebennierenrindenfunktion durch Gabe von Releasing-Hormonen und körperliche Belastung bei Patienten mit Adipositas.

In a clinical study on potential determinants underlying the impairment of growth hormone stimulation in obese human subjects, we examined in 20 otherwise healthy adult obese subjects (14 females, six males, age 18 to 40 years, body mass index greater than 29 kg/m2) the responses of growth hormone (hGH), adrenocorticotropic hormone (ACTH) and cortisol to releasing hormone stimulation (growth hormone-releasing hormone and corticotropin-releasing hormone) and the responses of hGH, ACTH, cortisol and free fatty acids (FFA) to physical exercise. Subjects with somatomedin-C levels less than or equal to 0.7 U/ml (group 1) were more obese than subjects with somatomedin-C levels greater than 0.7 U/ml (group 2) (p less than 0.01). In group 1, hGH increased by 4.3 +/- 1.2 ng/ml in response to releasing hormone administration and by 0.9 +/- 0.3 ng/ml in response to physical exercise (normal responses, increase by greater than 7 ng/ml), in group 2, hGH increased by 6.7 +/- 1.4, and 2.4 +/- 0.8 ng/ml, respectively (p less than 0.05 vs. group 1). Moreover, FFA stimulation by physical exercise was blunted in group 1 (p less than 0.05 vs. group 2). In contrast, ACTH stimulation was found increased in group 1 in comparison to group 2, particularly in response to physical exercise (p less than 0.01), and resulted in enhanced cortisol stimulation (p less than 0.05). Thus, impaired hGH stimulation in obese human subjects is not explained by an altered relationship between hGH and somatomedin-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

[The influence of autonomic diabetic neuropathy and human atrial natriuretic peptide on adrenal gland function in postural changes]. / Einfluss der autonomen diabetischen Neuropathie und des humanen atrialen natriuretischen Peptids auf das Verhalten der Nebennierenfunktion bei Anderung der Körperhaltung.

To investigate the influence of postural changes on plasma renin activity (PRA), plasma levels of human atrial natriuretic peptide (hANP) and on aldosterone in diabetes mellitus and autonomic neuropathy, ten patients with diabetes mellitus and autonomic neuropathy and ten patients with diabetes mellitus but without autonomic neuropathy were studied. Ten healthy subjects served as controls. Patients and controls were in supine position for 60 minutes, then changed posture sequentially to sitting (90 minutes) and to upright position (15 minutes). In controls, PRA was increased upon sitting and in the upright position, while hANP was decreased. Patients with autonomic neuropathy differed from controls in impaired renin stimulation, whereas in patients without autonomic neuropathy PRA responses to postural changes were only slightly decreased. In both groups of patients, the normal hANP responsiveness to postural changes was lacking. There were no differences in aldosterone levels between patients and controls. In patients with high basal hANP levels due to elevated systolic blood pressure renin responses to postural changes were decreased in comparison to those patients with low basal hANP levels. Thus, in patients with diabetes mellitus increased hANP levels which are not decreased in response to upright standing may contribute to the development of hyporeninism and its sequelae.

Role of atrial natriuretic factor in changes in the responsiveness of aldosterone to angiotensin II secondary to sodium loading and depletion in man.

1. Sodium loading blunts the response of aldosterone to infusion of angiotensin II, whereas sodium depletion leads to an enhanced response. The hypothesis was tested that these changes in responsiveness of the zona glomerulosa are mediated in part by changes in plasma atrial natriuretic factor levels. 2. To this end, plasma renin activity and plasma aldosterone were measured in the upright and recumbent position and during incremental infusions of angiotensin II (1, 3 and 6 ng of angiotensin II amide min-1 kg-1 for 1 h each dose) after 6 days of sodium loading (study 1), after 5 days of sodium depletion (study 2) and after sodium depletion plus infusion of atrial natriuretic factor (0.13 microgram/min for 8 h) on the test day (study 3). Six normal young males were investigated. 3. Plasma atrial natriuretic factor levels were around 5 pmol/l in study 2, 15 pmol/l in study 1 and 15 pmol/l in study 3 during infusion of atrial natriuretic factor. Two hours after the onset of atrial natriuretic factor infusion, plasma renin activity and plasma aldosterone (recumbent) were markedly and significantly lower in study 3 than in study 2, but still significantly higher than in study 1. The increase in plasma aldosterone after infusion of angiotensin II was slightly, but not significantly, blunted by infusion of atrial natriuretic factor in study 3 compared with study 2. The overall increase in plasma aldosterone was still significantly greater in study 3 than in study 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of renovascular hypertension by renal embolization.

Two cases with medically well-controlled renovascular hypertension due to unilateral contracted kidney were treated by percutaneous renal embolization. One of the patients had two aneurysms of the renal artery in addition to the stenosis. Both patients remained normotensive without medication after follow-ups of 6 and 24 months, respectively.

Does captopril reduce renal function in renovascular disease by postglomerular vasodilatation?

In hypertensive patients with bilateral renal artery stenosis (RAS) or RAS of a solitary kidney, reversible decrease of glomerular filtration rate (GFR) or acute renal failure has been observed following captopril administration. Decrease of GFR has been ascribed to preferential efferent vasodilatation. To test this hypothesis, acute changes of mean arterial pressure (MAP), renal plasma flow (RPF), GFR, plasma renin activity (PRA) and PGE2-excretion after 50 mg captopril orally were measured in post-transplant hypertensives with and without transplant renal artery stenosis (TRAS) during treatment with diuretics. The fall in MAP was similar in both groups; RPF did not change significantly; GFR decreased from 58 +/- 14 (s.d.) to 49 +/- 14 ml/min (TRAS, n = 8) and from 60 +/- 15 to 50 +/- 16 ml/min (without TRAS, n = 8). There was no evidence of postglomerular dilatation in patients with TRAS, and filtration fraction decreased only in patients without TRAS. Increase of PRA after captopril was not significantly different between the two groups. PGE2-excretion did not change significantly. In one patient with severe TRAS, long term angiotensin converting enzyme (ACE) inhibition and acute normalization of MAP with sodium nitroprusside both induced a comparable decrease of GFR. The results demonstrate that acute postglomerular vasodilatation does not necessarily occur after ACE inhibition in patients with TRAS and a high-renin state.

Hypotensive action of calcium antagonists as related to plasma noradrenaline and reactivity to noradrenaline.

From animal experiments it has been suggested that calcium antagonists owe their antihypertensive potency to a diminished sensitivity of the resistance vessels to circulating noradrenaline. We studied the effects of two calcium antagonists, nifedipine and verapamil, on blood pressure, reactivity to exogenous noradrenaline and plasma noradrenaline concentration in 10 patients with essential hypertension. In a cross-over comparison the patients were treated with nifedipine and verapamil for four weeks each. Both calcium antagonists led to a similar drop in arterial pressure. Resting plasma noradrenaline did not change during either treatment whereas a slight increase (P less than 0.05) in stimulated noradrenaline levels was observed during nifedipine treatment. The hypotensive effect of nifedipine was associated with a marked reduction (P less than 0.01) in the pressor effect of noradrenaline whereas no change in pressor response could be found during verapamil treatment. The results obtained suggest that an impairment of the pressor response to noradrenaline is not a general prerequisite for the antihypertensive action of calcium antagonists.

Influence of prostaglandin A1 on renal filtration, hemodynamics and excretion. Investigations in chronically instrumented conscious dogs on a low- and high-sodium diet.

The effect on renal function of a 210-min infusion of PGA1 into the aorta of 10 conscious beagle dogs has been investigated. In the sodium-replete group, PGA1 caused an increase in the glomerular filtration rate (GFR) (24%), renal blood flow (17%) and sodium excretion (20%). By contrast, in the sodium-depleted group, PGA1 caused a considerable reduction of GFR (25%) and sodium excretion (51%). In this group, baseline renal blood flow was lower, and there was no further reduction during PGA1 infusion. Fractional sodium excretion was unchanged in the sodium-replete dogs, but was reduced in the sodium-deplete state. Plasma renin activity was markedly elevated and further increased in the sodium-deplete group, but it was nearly unchanged in the sodium-replete group. This difference in renal response to exogenous PGA1 might be due to interaction with the renin-angiotensin system, which was markedly stimulated by sodium depletion and additionally by prostaglandin infusion.

The antihypertensive effect of captopril in severe essential, renovascular, renal and transplant renovascular hypertension.

The acute and long-term (6 months) effects of captopril (C) were studied in 23 patients with previously uncontrolled severe (DBP greater than 120 mmHg) hypertension of different origin: essential (EH,) n=10, renovascular (RVH) n=9, and renal (RH) n=4. In addition, four patients were treated with renal transplant artery stenosis and hypertension (TRVH), refractory to conventional therapy. Before treatment supine blood pressure (BP, mmHg) averaged: 205/131 (EH), 204/124 (RVH), 207/132 (RH) and 194/117 (TRVH). All patients received diuretics and other antihypertensive drugs, the dosages of which are expressed in arbitrary equivalent units (U) per day (UD = diuretics; UA = other antihypertensive drugs). Antihypertensive therapy before study: UD:EH 1.6; RVH 1.0; UA: EH 7.3; RVH 5.5. After admission, C dosage was increased from 25 mg to a maximum of 150 mg t.i.d. Antihypertensive treatment was reduced as far as possible. DBP decrease after 25 mg C was related to pretreatment PRA in RVH only. After 3 months of C treatment, BP decreased to 190/116 in EH and 145/89 in RVH (EH vs RVH P less than 0.01), 158/98 in RH, and 154/90 in TRVH. After 6 months, BP response was maintained in RH and TRVH. BP increased slightly in RVH to 158/102 mmHg, mainly because of impaired renal function in three patients with bilateral renovascular disease. In EH,BP decreased to 167/109, since three non-responders were taken out of the group. After 6 months, EH still received higher dosages of antihypertensive drugs than RVH. Acute and chronic hypotensive effects of C were not significantly correlated. Side-effects occurred in five patients: skin rash and pruritus [2], taste disturbances [1], proteinuria [1], and acute renal failure in one patient with TRVH. In our hands, captopril in combination with diuretics was significantly more potent in severe RVH than in EH. Dosages and side-effects of other antihypertensive drugs could be markedly reduced in most patients, which may improve long-term drug compliance.

Angiotensin II dependency of vascular resistance in the untouched kidney of renal hypertensive rats.

Renal hemodynamics following administration of the angiotensin II antagonist Saralasin were studied in untouched kidney of 11 two-kidney hypertensive rats and in kidneys of 7 control rats using an electromagnetic flowmeter. Renal blood flow (RBF) in controls averaged 6.2 +/- (SD) 1.7 vs. 5.2 +/- 0.9 ml/min/g kidney weight in the hypertensive group (n.s.). Renal vascular resistance (RVR) was significantly increased in untouched kidneys: 2.6 +/- 0.5 vs. 1.8 +/- 0.4 dyn . sec . cm-5 . 10(6) . g kidney weight-1. Following Saralasin infusion mean arterial blood pressure decreased significantly more in hypertensive rats. RBF increased by 24% in untouched kidneys vs. 12% in controls (p < 0.05), indicating a 34% decrease of RVR in hypertensive rats vs. 18% (p < 0.005) in controls. These results indicate that the increased RVR in untouched kidneys is highly dependent on circulating angiotensin II, which may reduce the antihypertensive role of the untouched kidney.

Goldblatt hypertension in rats: a model for unilateral renal artery stenosis in man.

Determinants of glomerular ultrafiltration were studied by micropuncture in clamped (n = 11) and unclamped (n = 7) kidneys of two-kidney hypertensive rats and compared to 15 controls. Infusion of the angiotensin II antagonist and saralasin lowered the blood pressure significantly. Glomerular capillary pressure (PGC) in clamped kidneys was decreased to 56 +/- (SD) 3 vs. 61 +/- 3 mm Hg in controls. Early proximal flow rate (EPFR) was decreased to 20 +/- 1 vs. 26 +/- 2 nl/min in controls, at an unchanged single nephron filtration fraction (SNFF), indicating a reduced glomerular plasma flow (SNGPF). Preglomerular resistance (RA) was increased by 21%. In unclamped kidneys PGC was increased to 65 +/- 2 mm Hg. EPFR was increased to 32 +/- 2 nl/min, indicating, at an unchanged SNFF, an increased SNGPF. RA increased by 51%, whereas postglomerular resistance declined by 25%. The ultrafiltration coefficient was reduced by 24% in unclamped kidneys. Our results indicate that in clamped kidneys an increase of RA causes a reduction of PGC and hence a reduction of pressure at the baroreceptor site which may act as a trigger mechanism for renin release.