Antihypertensive beta blocking action as related to renin and age: A pharmacologic tool to identify pathogenetic mechanisms in essential hypertension

Bühler, Fritz R.; Burkart, F; Lütold, B. E.; Küng, Markus; Marbet, G A; Pfisterer, Matthias

doi:10.1016/0002-9149(75)90168-x

Cited by 261 publications

(56 citation statements)

References 81 publications

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“…Therefore, the finding that vasorelaxation of Aff was much more prominent with a ␤ 1 -than with a ␤ 2 -or ␤ 3 -adrenergic receptor agonist would not be expected from Land's hypothesis. This may relate to a selective action of ␤ 1 -adrenergic receptors on the terminal renal Aff, where specialized granular smooth muscle cells are stimulated to release renin predominantly by ␤ 1 -adrenergic recep- tors (34,35). It seems that a similar receptor activation also induces vasorelaxation of this blood vessel.…”

Section: Discussionmentioning

confidence: 99%

β1 Receptors Protect the Renal Afferent Arteriole of Angiotensin-Infused Rabbits from Norepinephrine-Induced Oxidative Stress

Wang

José²,

Wilcox³

2006

Journal of the American Society of Nephrology

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Renal afferent arterioles (Aff) from angiotensin II (AngII)-infused rabbits have enhanced contractions to AngII that are normalized by tempol (superoxide dismutase mimetic), whereas contractions to norepinephrine (NE) are normal and unaffected by tempol. Tested was the hypothesis that ␤-receptor stimulation with NE prevents enhanced reactivity and superoxide generation. Preconstricted Aff from AngII-or vehicle-infused rabbits were perfused at physiologic pressure. Aff from vehicle-infused rabbits had strong, endothelium-independent relaxations to dobutamine (␤ 1 -receptor agonist; 78 ؎ 6%; P < 0.0001; mean ؎ SD) but only weak relaxations to salbutamol (␤ 2 -receptor agonist; 13 ؎ 3%; P < 0.05) or BRL-37,344 (␤ 3 -receptor agonist; 14 ؎ 3%; P < 0.05). Contractions to NE were similar in Aff from vehicle-and AngII-infused rabbits (؊36 ؎ 5 versus ؊34 ؎ 3%; NS) and were unaffected by tempol (؊32 ؎ 4%; NS). In contrast, phenylephrine contractions (␣ 1 agonist) were enhanced in Aff from AngII-infused rabbits (؊59 ؎ 6 versus ؊46 ؎ 4%; P < 0.05) and normalized by tempol. NE contractions in Aff from AngII-infused rabbits (؊34 ؎ 4%) were enhanced (P < 0.01) by propranolol (nonselective ␤ antagonist; ؊53 ؎ 6%), CGP-20,712A (selective ␤ 1 -receptor antagonist; ؊61 ؎ 9%), or Rp-cAMP (competitive inhibitor of cAMP; ؊56 ؎ 4%); were normalized by tempol; but were unaffected by ICI-118,551 (selective ␤ 2 -receptor antagonist) or SR-59,230A (selective ␤ 3 -receptor antagonist). Superoxide generation in Aff from AngII-infused rabbits that were assessed from ethidium:dihydroethidium was enhanced by addition of CGP-20,712A to NE but was normalized by tempol. Aff have robust ␣ 1 -receptor contraction and ␤ 1 -receptor dilation. NE elicits ␤ 1 signaling via cAMP that moderates oxidative stress and contractions in Aff from AngII-infused rabbits.J Moreover, administration of permanent SOD reverses hypertension in the AngII-induced but not the NE-induced rat model (3). They concluded that AngII selectively induces vascular oxidative stress, which contributes to hypertension. Relatively low rates of infusion of AngII into mice (4), rats (1,5,6), rabbits (7), or humans (8) increase BP gradually ("slow pressor response"). This is considered a model of human hypertension because the plasma levels of AngII increase only within a physiologic range of 50 to 100% (9). The hypertension entails a renal mechanism because it depends on salt intake (10) and an enhanced vascular reactivity of the renal afferent arteriole (Aff) to AngII (11). Unlike AngII, infusion of NE leads to tachyphylaxis and a decreased BP response (8). The AngII slow pressor response has been related to ROS because it is prevented by co-infusion of the permeant SOD mimetic nitroxide tempol (4,6).Low rates of infusion of the thromboxane-prostanoid receptor (TP-R) mimetic U-46,619 (12) or endothelin-1 (ET-1) (13) also elicit slow pressor responses that are accompanied by oxidative stress. Moreover isolated, pressurized Aff that are dissected from the kidneys of rabbits that are und...

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Section: Discussionmentioning

confidence: 99%

β1 Receptors Protect the Renal Afferent Arteriole of Angiotensin-Infused Rabbits from Norepinephrine-Induced Oxidative Stress

Wang

José²,

Wilcox³

2006

Journal of the American Society of Nephrology

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“…Five patients were classified as normalrenin and one as a high-renin type; low-renin patients were excluded because their ,B-adrenoreceptor responsiveness may be reduced. 27 Endocrine disorders were excluded in all patients; the female patient did not take estrogen-containing contraceptive pills. All patients gave informed consent.…”

Section: Methodsmentioning

confidence: 99%

Lack of beta-adrenoreceptor hypersensitivity after abrupt withdrawal of long-term therapy with oxprenolol.

Bolli¹,

Bühler²,

Raeder³

et al. 1981

Circulation

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SUMMARY The possibility of j-adrenoreceptor hypersensitivity after abrupt withdrawal of long-term therapy (8-18 months) with the slow-release (SR) formulation of oxprenolol (160-320 mg/day) was assessed in six patients with uncomplicated essential hypertension. The chronotropic dose 25 of isoproterenol (the dose that increases the resting heart rate by 25 beats/min), plasma concentration of catecholamines, triiodothyronin and thyroxin, plasma renin activity and aldosterone, hemoglobin, hematocrit and oxyhemoglobin dissociation were measured on the last day of oxprenolol SR intake and 1, 2, 3, 6 and 13 days after abrupt replacement by identical placebo tablets. The chronotropic dose 25 of isoproterenol (gg/m'), which was greater than 25.6 in all patients on the last day of oxprenolol SR, fell to 4.83 + 2.03 on the second day and to 3.50 on the third day after its abrupt withdrawal and reached a minimal value on the thirteenth day (2.78 ± 0.30). Throughout the study, plasma concentrations of catecholamines, triiodothyronin and thyroxin and oxyhemoglobin dissociation remained unchanged. Plasma renin activity and plasma aldosterone, which were suppressed during oxprenolol administration, rose significantly during placebo, coinciding with a significant fall in hematocrit and hemoglobin. No major subjective symptoms were reported by the patients. Thus, hypersensitivity of i-adrenoreceptor-mediated responses was not demonstrated after sudden withdrawal of oxprenolol SR.

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“…Younger white hypertensive patients tend to have higher levels of renin and angiotensin II, and available evidence points to starting such patients on a drug that inhibits the renin-angiotensin system for optimal blood pressure lowering. [15][16][17][18] However, such drugs are less K Reduce blood pressure to o140 and o85 mmHg, and lower for patients with diabetes K This extrapolation to lower blood pressure should probably also apply to other groups at high cardiovascular risk (eg poststroke, renal disease) Figure 1 Modified Cambridge AB/CD Rule. Initial monotherapy (step 1) is selected according to age and ethnic group, as surrogates for plasma renin.…”

Section: First-line Therapymentioning

confidence: 99%

Better blood pressure control: how to combine drugs

et al. 2003

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Antihypertensive beta blocking action as related to renin and age: A pharmacologic tool to identify pathogenetic mechanisms in essential hypertension

Cited by 261 publications

References 81 publications

β1 Receptors Protect the Renal Afferent Arteriole of Angiotensin-Infused Rabbits from Norepinephrine-Induced Oxidative Stress

β1 Receptors Protect the Renal Afferent Arteriole of Angiotensin-Infused Rabbits from Norepinephrine-Induced Oxidative Stress

Lack of beta-adrenoreceptor hypersensitivity after abrupt withdrawal of long-term therapy with oxprenolol.

Better blood pressure control: how to combine drugs

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