P3568The relationship between plasma renin and aldosterone levels and the reduction of blood pressure with spironolactone in patients with resistant hypertension

Abstract The group of patients with resistant hypertension (RH) is not homogeneous on concentration of renin and aldosterone (AS). A lot of studies have shown that spironolactone (SP) was by far the most effective blood pressure-lowering treatment for patients with RH. However, it has been unknown whether SP would be the most effective in patients with different plasma renin profile. The aim was to determine whether plasma renin and AS predict the most effective treatment of SP. Methods 79 patients with RH were included in the study (a mean of 3.4±1.4 drugs per patient including diuretic, ACE-I or an ARB). The plasma AS and active renin concentration (ARC), the plasma aldosterone-to-renin ratio (ARR) were estimated at baseline. After chemical evaluation patients started on SP treatment with a mid-dose 25 mg daily (range 12.5–50 mg). At baseline and after 12 weeks of therapy patients underwent clinic and 24-hour BP measurement, also hematocrit, potassium (K), serum creatinine (C), eGFR were checked. Results In patients with RH the ARC varied widely and they were divided into low 46%, normal 29% and high renin 25% subgroups. All groups of patients had similar AS levels. Patients with high renin hypertension (HRH) had significantly worse renal function than patients with low renin (LRH) or normal renin hypertension (NRH), also hematocrit were significantly higher in HRH patients than in patients with LRH and NRH. At baseline in patients with RH was an excellent correlation between ARC and eGFR (P<0.001). After SP in whole group, the change from baseline in the clinic BP was −13.4/−6.8 mm Hg (P<0.0001 for both) and in 24-hour BP was −10.6/−6.1 mm Hg (P<0.001 for both), but patients with HRH showed less efficacy than patients with LRH and NRH (−5.4/−3.1 mm Hg; P<0.05 for both) and in 24-hour BP was −4.8/−2.9 mm Hg (P<0.05 for both). Moreover, in HRH patients the hematocrit and C levels increased significantly after the start of SP (P<0.001; P<0.0001 respectively). By regression analysis in whole group patients RH ARC and AS levels were not associated with the changes in BP, only eGFR was significantly associated with BP change for DBP (0.391, P<0.05); in patients with LRH and NRH was a mild relation between the change for SBP and ARR (P<0.05 for both), but not for HRH patients. Conclusion SP showed additional antihypertensive effect in the whole group of patients with RH, but in patients with HRH was less effective than in patients with LRH and NRH and lead to the worsening of renal function. In the whole group of patients with RH plasma renin and aldosterone levels were not associated with BP response to SP, but the change in DBP was correlated with baseline eGFR. Only in patients with LRH and NRH was a mild association between BP response to SP and ARR. So, we can't treat all RH patients with the help of one universal algorytm and treatment should be tailored to each patient according to neurohumoral profile and renal function.

Download Full-text

Case Report: Segmental Arterial Mediolysis, a Rare Cause of Hypertension

Canadian Journal of Kidney Health and Disease ◽

10.1177/2054358120950885 ◽

2020 ◽

Vol 7 ◽

pp. 205435812095088

Author(s):

Jieqing Jessica Xu ◽

Pasteur Rasuli ◽

Kevin D. Burns

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Resistant Hypertension ◽

Blood Pressure Monitoring ◽

Plasma Renin ◽

Pressure Control ◽

Home Blood Pressure ◽

Elevated Plasma ◽

Vascular Events ◽

Segmental Arterial Mediolysis

Rationale: The differential diagnosis for hypertension with elevated plasma renin is broad. This case illustrates one of the rarer, and therefore underrecognized, causes of high renin hypertension. Presenting concerns of the patient: A 41-year-old man with a medical history significant for multiple ischemic strokes and dyslipidemia presented for assessment of decreased renal function and resistant hypertension. His initial workup for secondary causes of hypertension was remarkable for an elevated plasma renin and normal aldosterone. Further investigation with computed tomography (CT) angiography was performed, which demonstrated multiple bilateral renal aneurysms and infarcts. Diagnoses: After ruling out other potential causes of bilateral renal aneurysms and infarcts, a diagnosis of segmental arterial mediolysis (SAM) was made. Interventions: Optimization of antihypertensive regimen, counseling regarding regular home blood pressure monitoring, and smoking cessation. Outcomes: The patient achieved excellent blood pressure control, stable renal function, and had no further strokes or other vascular events. Teaching points: Our case demonstrates the importance of considering SAM in the diagnosis of hypertension with elevated plasma renin and as a vasculitis mimic. It also highlights the importance of considering renal vascular imaging in the workup of resistant hypertension.

Download Full-text

Blood Pressure-Lowering Effect of Wine Lees Phenolic Compounds Is Mediated by Endothelial-Derived Factors: Role of Sirtuin 1

Antioxidants ◽

10.3390/antiox10071073 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1073

Author(s):

Raúl López-Fernández-Sobrino ◽

Jorge R. Soliz-Rueda ◽

Javier Ávila-Román ◽

Anna Arola-Arnal ◽

Manuel Suárez ◽

...

Keyword(s):

Blood Pressure ◽

Antihypertensive Effect ◽

Sirtuin 1 ◽

Dependent Manner ◽

Blood Pressure Lowering Effect ◽

Synthesis Inhibitor ◽

Spontaneously Hypertensive ◽

Lowering Effect ◽

Pressure Lowering ◽

Endothelial Gene Expression

The antihypertensive effect of wine lees powder (WLPW) from a Cabernet grape variety was related to its high content in flavanols and anthocyanins compounds. This study investigates the involvement of endothelial-derived factors and SIRT1 in its bioactivity. Spontaneously hypertensive rats (SHR) were orally administered water or WLPW (125 mg/kg bw). Posteriorly, both groups were intraperitoneally administered saline, Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthesis inhibitor, indomethacin, a prostacyclin synthesis inhibitor, or sirtinol, an inhibitor of sirtuins. Blood pressure (BP) was recorded before and 6 h after WLPW administration. In an additional experiment, SHR were administered water or WLPW and endothelial expressions of eNos, Sirt1, Nox4, and Et1 were determined. The BP-lowering properties of WLPW were abolished by L-NAME and partially reduced by indomethacin, demonstrating that WLPW antihypertensive effect was mediated by changes in NO availability, although prostacyclin also contributed to this activity. Moreover, BP-lowering effect was reduced by sirtinol, indicating that WLPW decreased BP in a SIRT1-dependent manner. Furthermore, WLPW upregulated eNos and Sirt1 and downregulated Nox4 and Et1 endothelial gene expression. These results evidence the vasoprotective effect of WLPW and show that its antihypertensive effect in SHR is endothelium dependent and mediated by SIRT1.

Download Full-text

Enhancement of the Antihypertensive Effect of Hydrochlorothiazide in Dogs after Suppression of Renin Release by Beta-Adrenergic Blockade

Clinical Science ◽

10.1042/cs0480147 ◽

1975 ◽

Vol 48 (2) ◽

pp. 147-151

Author(s):

C. S. Sweet ◽

M. Mandradjieff

Keyword(s):

Blood Pressure ◽

Plasma Renin Activity ◽

Arterial Blood Pressure ◽

Antihypertensive Effect ◽

Plasma Renin ◽

Renin Activity ◽

Renin Release ◽

Antihypertensive Activity ◽

Adrenergic Blockade ◽

Arterial Blood

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.

Download Full-text

Antihypertensive Property and Renal Protection by Shichimotsu-koka-to Extract in Salt-induced Hypertension in Dahl Strain Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x94000073 ◽

1994 ◽

Vol 22 (01) ◽

pp. 51-62 ◽

Cited By ~ 6

Author(s):

Nobuhito Hiwara ◽

Yoshio Uehara ◽

Satoru Takada ◽

Yukari Kawabata ◽

Nobuko Ohshima ◽

...

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Aortic Wall ◽

Antihypertensive Effect ◽

Blood Pressure Reduction ◽

Glomerular Sclerosis ◽

Pressure Reduction ◽

Renal Protection ◽

Induced Hypertension ◽

Sclerotic Lesions

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsu-koka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Download Full-text

Effects of Indomethacin Alone and during Diuretic or β-Adrenoreceptor-Blockade Therapy on Blood Pressure and the Renin System in Essential Hypertension

Clinical Science ◽

10.1042/cs055203s ◽

1978 ◽

Vol 55 (s4) ◽

pp. 203s-205s ◽

Cited By ~ 12

Author(s):

J. A. Lopez-Ovejero ◽

M. A. Weber ◽

J. I. M. Drayer ◽

J. E. Sealey ◽

J. H. Laragh

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Water Retention ◽

Antihypertensive Effect ◽

Renin Secretion ◽

Blood Pressure Lowering ◽

Blood Pressure Lowering Effect ◽

Uncomplicated Hypertension ◽

Pressure Lowering ◽

Propranolol Therapy

1. Indomethacin was administered alone or in addition to either diuretic or propranolol therapy to three groups of patients with essential hypertension on a free sodium diet. 2. Indomethacin administration reduced renin secretion by about 30% in untreated uncomplicated hypertensive patients and by about 75% in those whose renin secretion had either been stimulated or suppressed by maintained diuretic or β-adrenoreceptor-blockade therapy. 3. Indomethacin administration produced no net effect on blood pressure in untreated patients with uncomplicated hypertension but it blunted or reversed the antihypertensive effect of either diuretic or propranolol therapy. 4. Salt and water retention may be an important factor in the blood pressure-raising effect of indomethacin during diuretic or propranolol therapy: In addition, prostaglandin synthesis may be important in counteracting increased α-adrenergic tone, which may limit the blood pressure-lowering effect of β-adrenoreceptor-blockade. 5. Because of these interactions and their pressor potential indomethacin should be used with caution when combined with either diuretics or β-adrenoreceptor blockers.

Download Full-text

Adherence to Blood Pressure–Lowering Drugs and Resistant Hypertension: Should Trial of Direct Observation Therapy Be Part of Preassessment for Renal Denervation?

Canadian Journal of Cardiology ◽

10.1016/j.cjca.2013.07.678 ◽

2013 ◽

Vol 29 (12) ◽

pp. 1741.e1-1741.e3 ◽

Cited By ~ 9

Author(s):

Marcel Ruzicka ◽

Brendan McCormick ◽

Frans H.H. Leenen ◽

Michael Froeschl ◽

Swapnil Hiremath

Keyword(s):

Blood Pressure ◽

Direct Observation ◽

Resistant Hypertension ◽

Renal Denervation ◽

Blood Pressure Lowering ◽

Pressure Lowering

Download Full-text

The Use of Frusemide and Propranolol in the Treatment of the Hypertension of Chronic Renal Disease

Scottish Medical Journal ◽

10.1177/00369330740190s106 ◽

1974 ◽

Vol 19 (1_suppl) ◽

pp. 25-32 ◽

Cited By ~ 2

Author(s):

R. Wilkinson ◽

Mary Pickering ◽

Valerie Robson ◽

R. W. Elliott ◽

D. N. S. Kerr

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Renal Disease ◽

Serum Creatinine ◽

Marked Reduction ◽

Chronic Renal Disease ◽

Plasma Renin ◽

Sodium Retention ◽

Exchangeable Sodium ◽

Standing Blood Pressure

Nine patients with renal disease, hypertension and impairment of renal function of varying degree have been studied before and during treatment with frusemide. In three patients observations were repeated following the addition of propranolol. In most cases frusemide resulted in a reduction of both lying and standing blood pressure but for the group the fall was not significant (P>0.05). In all patients a reduction in exchangeable sodium was achieved and the fall was significant for the group (P<0.05); this was accompanied by a significant increase in serum creatinine (P < 0.05). Plasma renin activity was increased in all patients during treatment with frusemide and the change for the group was significant (P<0.05). The addition of propranolol resulted in a marked reduction in renin in the three patients treated but in two blood pressure actually rose; in these two sodium retention had occurred following the introduction of propranolol.

Download Full-text