Abstract 641: Renal Denervation does not Lower Blood Pressure in Spontaneously Hypertensive Rats Treated with a Beta-1 Adrenergic Receptor Antagonist.

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Jeremiah Phelps ◽  
Gregory Fink
Keyword(s):  
Blood Pressure ◽  
Adrenergic Receptor ◽  
Renal Denervation ◽  
Blood Pressure Response ◽  
Beta Blockers ◽  
Antihypertensive Drug Therapy ◽  
Spontaneously Hypertensive ◽  
Adrenergic Antagonist ◽  
Before And After ◽  
Pre Treatment

We have used the SHR as an animal model to understand how renal denervation (RDN) lowers blood pressure. In order to determine how concomitant antihypertensive drug therapy could affect the blood pressure response to RDN, we performed RDN both before and after chronic (several days) treatment via the drinking water with the selective alpha-1 adrenergic antagonist prazosin and the selective beta-1 adrenergic antagonist atenolol. In the presence of prazosin treatment, RDN (n=7) significantly (p<0.05) lowered mean arterial pressure (MAP) compared to sham operated (SO; n=6) SHR (Δ=–4.0±1.7mmHg in RDN-SHR vs +1.5±1.3 in SO-SHR). Subsequent addition of atenolol during prazosin treatment reduced MAP significantly in both groups, but MAP in SO-SHR fell to the same level as in RDN-SHR, i.e. the antihypertensive effect of RDN was lost. After discontinuation of all drug treatment, the change in MAP from pre-treatment baseline was –7.7±3.5mmHg in RDN-SHR and +3.0±4.0mmHg in SO-SHR, p=0.06). To test whether the BP response to RDN would be lost during blockade of beta-1 adrenergic receptors alone, we performed RDN in SHR (n=5) pre-treated with atenolol. Atenolol alone significantly reduced MAP (Δ=-20.7±2.5mmHg). Steady-state MAP was not further reduced by RDN (Δ=+2.1±0.9mmHg). When atenolol was withdrawn MAP rose but remained reduced from baseline (Δ= -9.5±0.9mmHg). This magnitude of BP reduction is comparable to what we have previously observed after RDN in untreated SHR. In summary, in SHR RDN does not lower BP in the presence of an effective antihypertensive dose of a beta-1 antagonist. This indicates that RDN is reducing BP in SHR by interrupting a mechanism also affected by beta-1 adrenergic receptor signaling. Although further investigation is necessary, the data suggest that possibility that patients on clinically effective antihypertensive doses of beta-blockers may not exhibit a good response to RDN.

scholarly journals Predictors of blood pressure response after renal denervation beyond pretreatment blood pressure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Schmieder ◽  
C Delles ◽  
L Lauder ◽  
C Ott ◽  
M Boehm ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Renal Denervation ◽  
Antihypertensive Drugs ◽  
Blood Pressure Response ◽  
Methodological Approach ◽  
Large Degree ◽  
Initial Value ◽  
Study Population ◽  
Pre Treatment

Abstract Background The principle of initial value (Wilder's law of initial value) proposes that the “direction of response of body function to any agent depends to a large degree on the initial value of that function”. Indeed, in several trials on renal denervation (RDN), pre-treatment blood pressure (BP) has been consistently and repeatedly found to predict the decrease in BP after RDN. Efforts to discover further statistically significant and clinically meaningful predictors of BP response to RDN failed. Objective By use of a new methodological approach, we aimed to determine predictors of BP response after RDN in patients with resistant hypertension. Methods The study population comprised 266 patients with resistant hypertension (mean age 62 years, 34% females, mean BMI 30.5 kg/m2, 27% had coronary heart disease, 42% had diabetes mellitus and 61% had hypercholesterolaemia) who underwent radiofrequency RDN with the Symplicity catheter at the Universities of Homburg and Erlangen. Clinical data including 24h ambulatory BP (ABP) were obtained prior to, and 3, 6 and 12 months after RDN. The primary parameter of response was defined as change in 24-hour systolic ABP after 6 months from pre-treatment values. As expected, change in 24h systolic ABP correlated with pre-treatment 24h systolic ABP (r2 linear = 0.225, p&lt;0.001), with change in 24h systolic ABP = 73.82 + 0.55 x pre-treatment 24h systolic ABP. To overcome the predominant role of the pre-treatment BP that may mask other factors, we calculated for each individual patient the “expected systolic ABP decrease” by applying this regression equation and the “excessive systolic ABP decrease” by subtracting the measured from expected change in 24h systolic ABP. We divided the study population into 2 groups (above [responders] and below [non-responders] of the median change in excessive 24h systolic ABP. Results Neither pre-treatment 24h systolic or diastolic ABP, nor office systolic or diastolic BP differed between the two groups (all p&gt;0.20). Following RDN, 24h systolic ABP decreased in the responders by −23.3±16 vs non-responders +1.4±11 mmHg at 6 month, and 24h systolic ABP values were also significantly lower in responders at 3 and 12 months (all p&lt;0.001), without difference in number of antihypertensive drugs between the groups. Of all clinical variables at baseline, office heart rate (65.6 vs 68.7±12 bpm, p=0.024) and HbA1c (6.07±0.88 vs. 6.37±1.23%, p=0.035) were lower in responders compared with non-responders. Finally, a multiple regression analysis confirmed that pre-treatment 24h systolic ABP (beta +0.565, p&lt;0001), HbA1c (beta −0.167, p=0.004) and office HR (beta +0.106, p=0.057) were independent predictors of decrease in 24h systolic ABP. Conclusion In patients with resistant hypertension, lower HbA1c and office HR were identified as predictors of BP response in addition to pre-treatment BP. This finding may help to identify hypertensive patients who benefit most from RDN. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Extramural grant provided vy Medtronic INc

Effects of renal denervation on cardiovascular response to furosemide in conscious lambs

1995 ◽  
Vol 269 (1) ◽  
pp. H149-H152 ◽  
Author(s):  
F. G. Smith ◽  
A. M. Strack
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Renal Denervation ◽  
Cardiovascular Response ◽  
Blood Pressure Response ◽  
Sympathetic Nerves ◽  
Renal Nerves ◽  
Before And After ◽  
Renal Sympathetic

The cardiovascular response to furosemide in the newborn and the role of renal sympathetic nerves in influencing this response have not been investigated. We hypothesized that in conscious lambs, furosemide would decrease blood pressure, the response being accentuated in the absence of renal sympathetic nerves. Pulsatile pressures and heart rates were measured before and after furosemide (2 mg/kg) administration to chronically instrumented lambs with either bilateral renal denervation (denervated, n = 8) or renal nerves intact (intact, n = 6). In intact lambs, mean arterial pressure remained constant after furosemide; in denervated lambs there was an increase in arterial pressure 20 min after furosemide (P < 0.001), and control levels were reached by 100 min. Basal heart rate was higher in denervated than in intact lambs (P = 0.009). In both groups of lambs, heart rate increased 40 min after furosemide and remained elevated. These data provide new information that, in conscious newborn animals, renal sympathetic nerves influence the blood pressure response to furosemide, as well as basal control of heart rate.

scholarly journals Effect of blood pressure on L-NAME-sensitive component of vasorelaxation in adult rats

2007 ◽  
pp. S77-S84
Author(s):  
A Púzserová ◽  
Z Csizmadiová ◽  
I Bernátová
Keyword(s):  
Blood Pressure ◽  
Femoral Artery ◽  
Spontaneously Hypertensive Rats ◽  
No Production ◽  
Hypertensive Rats ◽  
Adult Rats ◽  
Spontaneously Hypertensive ◽  
Before And After ◽  
Pre Treatment ◽  
Wistar Kyoto

The aim of this study was to investigate nitric oxide (NO) production and L-NAME-sensitive component of endothelium-dependent vasorelaxation in adult normotensive Wistar-Kyoto rats (WKY), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). Blood pressure (BP) of WKY, BHR and SHR (determined by tail-cuff) was 111+/-3, 140+/-4 and 184+/-6 mm Hg, respectively. NO synthase activity (determined by conversion of [(3)H]-L-arginine) was significantly higher in the aorta of BHR and SHR vs. WKY and in the left ventricle of SHR vs. both BHR and WKY. L-NAME-sensitive component of endothelium-dependent relaxation was investigated in the preconstricted femoral arteries using the wire myograph during isometric conditions as a difference between acetylcholine-induced relaxation before and after acute N(G)-nitro-L-arginine methyl ester pre-treatment (L-NAME, 10(-5) mol/l). Acetylcholine-induced vasorelaxation of SHR was significantly greater than that in WKY. L-NAME-sensitive component of vasorelaxation in WKY, BHR and SHR was 20+/-3 %, 29+/-4 % (p<0.05 vs. WKY) and 37+/-3 % (p<0.05 vs. BHR), respectively. There was a significant positive correlation between BP and L-NAME-sensitive component of relaxation of the femoral artery. In conclusion, results suggest the absence of endothelial dysfunction in the femoral artery of adult borderline and spontaneously hypertensive rats and gradual elevation of L-NAME-sensitive component of vasorelaxation with increasing blood pressure.

scholarly journals Difference on blood pressure response of spontaneously hypertensive and normotensive rats-(1)-

1967 ◽  
Vol 63 (6) ◽  
pp. 472-486 ◽  
Author(s):  
Riitiro IWAKI ◽  
Yoshitaka KUDO ◽  
Juniti ISIKO ◽  
Tsutomu IRIKURA
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Response ◽  
Pressure Response ◽  
Spontaneously Hypertensive

scholarly journals Decreased blood pressure response in mice deficient of the  1b-adrenergic receptor

1997 ◽  
Vol 94 (21) ◽  
pp. 11589-11594 ◽  
Author(s):  
A. Cavalli ◽  
A.-L. Lattion ◽  
E. Hummler ◽  
M. Nenniger ◽  
T. Pedrazzini ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adrenergic Receptor ◽  
Blood Pressure Response ◽  
Pressure Response

scholarly journals A Japan nationwide web-based survey of patient preference for renal denervation for hypertension treatment

2021 ◽  
Author(s):  
Kazuomi Kario ◽  
Hideaki Kagitani ◽  
Shoko Hayashi ◽  
Satsuki Hanamura ◽  
Keisuke Ozawa ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Drug Therapy ◽  
Side Effects ◽  
Antihypertensive Drug ◽  
Patient Preference ◽  
Renal Denervation ◽  
Antihypertensive Drugs ◽  
Japanese Patients ◽  
Home Blood Pressure ◽  
Antihypertensive Drug Therapy

AbstractRenal denervation is a potential alternative to antihypertensive drug therapy. However, data on patient preference for this treatment option are limited and there are no data specifically from Asian patients. This study evaluated patient preference for renal denervation in patients with hypertension from Japan. Patients were a subset of those who participated in a March 2020 online electronic survey of patients with hypertension who had regularly visited medical institutions for treatment, were receiving antihypertensive drug therapy and had home blood pressure recordings available. The survey included a question about patient preference for treatment with renal denervation. A total of 2,392 patients were included (66% male, mean age 59.8 ± 11.6 years, mean duration of hypertension 11.4 ± 9.5 years). Preference for renal denervation was expressed by 755 patients (31.6%), and was higher in males than in females, in younger compared with older patients, in those with higher versus lower blood pressure, in patients who were less adherent versus more adherent to antihypertensive drug therapy, and in those who did rather than did not have antihypertensive drug-related side effects. Significant predictors of preference for renal denervation on logistic regression analysis were younger patient age, male sex, higher home or office systolic blood pressure, poor antihypertensive drug adherence, the presence of heart failure, and the presence of side effects during treatment with antihypertensive drugs. Overall, a relevant proportion of Japanese patients with hypertension expressed a preference for renal denervation. This should be taken into account when making shared decisions about antihypertensive drug therapy.

Blood pressure responsiveness during the development of hypertension in the conscious spontaneously hypertensive rat

1985 ◽  
Vol 63 (10) ◽  
pp. 1258-1262 ◽  
Author(s):  
Corey B. Toal ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Blood Pressure Response ◽  
Receptor Occupancy ◽  
Pressure Response ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Freely Moving ◽  
Wistar Kyoto

Blood pressure responsiveness to iv noradrenaline and angiotensin II was studied in conscious, freely moving, age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 to 16 weeks of age. At 4 and 6 weeks the SHR showed small, but nonsignificant increases in responsiveness compared with WKY to both noradrenaline and angiotensin II. At 8 weeks they exhibited similar responses to the WKY. Subsequently, at 12 and 16 weeks decreased responsiveness to noradrenaline (nonsignificant) and angiotensin II (p < 0.05 at 12 and 16 weeks) was observed in SHR versus WKY. At 16 weeks of age, hexamethonium caused potentiation of the blood pressure response to noradrenaline and angiotensin II, but to the same degree in the two strains. Captopril at this age did not elicit potentiation to noradrenaline or angiotensin II in either strain. These results indicate that there is no rise in blood pressure responsiveness to circulating pressor agents, parallel to the development of hypertension in SHR. Increased receptor occupancy or more active attenuating reflexes in SHR versus WKY appear not to be involved in the absence of hyperresponsiveness in intact consious SHR at 16 weeks of age.

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