Indirect evidence for vascular uptake of circulating renin in hypertensive patients.

Taddei, Stefano; Virdis, Agostino; Abdel-Haq, B.; Giovannetti, Roberto; Duranti, P.; Arena, A.; Favilla, Stefania; Salvetti, Antonio

doi:10.1161/01.hyp.21.6.852

Cited by 16 publications

(8 citation statements)

References 22 publications

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“…This diplotype is associated with Ϸ32% of the LR hypertensive subjects in our cohort. Although defects in ␤ 2 AR expression and functionality have been associated with LR hypertension in a few studies, 49,50 to our knowledge, no previous data exist concerning the involvement of ␤ 2 AR genetic variability in the determination of this intermediate phenotype. As is true for genetic analyses of all complex traits, such as LR hypertension, it is possible that other genes, in addition to the ␤ 2 AR, contribute to the intermediate phenotype that we define as the ␤ 2 AR LR phenotype.…”

Section: Discussionmentioning

confidence: 96%

β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension

et al. 2006

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Abstract-Two genetic variants of the ␤-2 adrenergic receptor, 46GϾA and 79CϾG, affect agonist-mediated receptor downregulation and vascular reactivity. We determined whether these variants were associated with hypertension, per se, blood pressure response to dietary sodium, 2 forms of salt-sensitive hypertension (low renin and nonmodulation), and the activity of the renin-angiotensin-aldosterone system. Included are 280 hypertensive and 65 normotensive white subjects who had the 2 ␤-2 adrenergic receptor genotypes available. Of all subjects, 171 hypertensive and 48 normotensive subjects had complete data for intermediate phenotyping and blood pressure evaluation on high-and low-sodium balance. The ␤-2 adrenergic receptor variants were not associated with hypertension per se. However, among hypertensive subjects, the change (from low to high sodium balance) in mean arterial pressure differed significantly by genotype and by diplotype. Compared with all of the other diplotypes combined, 46AA/79CC was associated with a greater change in blood pressure. Furthermore, this diplotype was associated with low-renin (LR) hypertension (identifying 32% of the LR hypertensives), higher plasma aldosterone, and lower plasma renin and serum potassium levels. In conclusion, the 46AA/79CC diplotype is associated with greater blood pressure response to dietary sodium and higher odds of LR hypertension. We propose that the mechanism for the observed association is inadequate suppression of aldosterone with salt intake, implicating the ␤-2 adrenergic receptor in the regulation of aldosterone secretion. This hypothesis was confirmed in isolated glomerulosa cells, where ␤-2 adrenergic receptor stimulation increased aldosterone secretion, whereas blockade reduced the stimulated aldosterone response. Key Words: ␤-2 adrenergic receptor Ⅲ hypertension Ⅲ salt-sensitive hypertension Ⅲ low-renin hypertension Ⅲ single nucleotide polymorphisms Ⅲ haplotypes Ⅲ diplotypes T he ␤ 2 -adrenergic receptor (␤ 2 AR) is generally thought to influence blood pressure homeostasis through sympathetic nervous system-mediated effects on vascular tone and cardiac contractility. 1 The ␤ 2 AR gene is located on the distal segment of the long arm of chromosome 5 (5q33.3 to 34); this region has been identified as a susceptibility locus for blood pressure and hypertension in several genome-wide scans. [2][3][4][5] Two common, nonsynonymous, coding single nucleotide polymorphisms (SNPs) from this gene, 46GϾA (Gly16Arg) and 79CϾG (Gln27Glu), have been shown to affect agonistmediated receptor desensitization and downregulation, 6 -8 as well as vascular reactivity. 9 -11 Because of these findings, these and other polymorphisms in the ␤ 2 AR gene have been extensively investigated in linkage and association studies with human hypertension, with conflicting results. 10 -24 As has been observed with other complex diseases, conflicting findings have been the norm in genetic studies of hypertension, particularly when a distant phenotype (eg, hypertension) has been used. 25...

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Section: Discussionmentioning

confidence: 96%

β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension

et al. 2006

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“…However, the finding that plasma levels of bradykinin generally parallel those of the reninangiotensin system [24] does not support this hypothesis. Another possibility is represented by the hypothetical activity of the drug on a vascular reninangiotensin system [11,12,18], since in spontaneously hypertensive rats at least part of the antihypertensive effect of captopril is determined by the ability of the drug to inhibit vascular angiotensin II formation [25]. However, this possibility can only be hypothesised in humans and it needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma angiotensin II (pg.ml -~) was determined by radioimmunoassay after extraction of the peptide from plasma by Sep-Pak C18 and purification following reversed-phase HPLC. Details of the method have been described previously [11,12].…”

Section: Analytical Proceduresmentioning

confidence: 99%

Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients

Taddei

Ghiadoni

Mattei

et al. 1995

Eur J Clin Pharmacol

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Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.

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“…Plasma Ang II (pg/ml) was determined by radioimmunoassay after extraction of the peptide from plasma with Sep-Pak C18 cartridges [3]. This procedure was previously described [3] and validated by measurement with high-performance liquid chromatography of purified Ang II [5]. In our laboratory, the plasma level of purified Ang II in healthy subjects is 13.4 AE 7.9 pg/ml (range 3.3-34.8 pg/ml).…”

Section: Analytical Proceduresmentioning

confidence: 99%

“…More recently, the existence of a vascular RAS has been proposed in human hypertension. Thus it has been demonstrated that infusion into the brachial artery of isoproterenol, a selective agonist of b-adrenergic receptors, causes the release of active and inactive renin and of angiotensin II (Ang II) in the forearm vessels of essential hypertensive patients [3][4][5][6][7]. This local release is closely related to the circulating renin profile [5].…”

Section: Introductionmentioning

confidence: 99%

Relationship between the Circulating and Vascular Renin-Angiotensin System and the Vasodilating Effect of Captopril in Human Hypertension

Virdis

Ghiadoni²,

Favilla³

et al. 1999

Blood Pressure

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Virdis A, Ghiadoni L, Favilla S, Duranti P, Taddei S, Salvetti A. Relationship between the circulating and vascular renin-angiotensin system and the vasodilating effect of captopril in human hypertension. Blood Pressure 1999; 8: 85-93.A vascular renin-angiotensin system (RAS) is present in the forearm vasculature of essential hypertensive patients and is closely related to the circulating renin profile. To test whether the haemodynamic effect of acute intrabrachial administration of captopril is related to the circulating and/or vascular RAS, 31 hypertensive patients were selected and divided into four groups according to their different circulating RAS profile (n = 7 hypertensive patients with primary aldosteronism and suppressed plasma renin activity; n = 7 low renin essential hypertensive patients; n = 8 normal renin essential hypertensive patients; n = 9 high renin renovascular hypertensive patients). The forearm net balance of active renin, plasma renin activity and angiotensin II, obtained by intrabrachial infusion of the b-adrenergic receptor agonist isoproterenol (0.03, 0.1, 0.3 mg/100 ml/min) and calculated as the product of the venous-arterial plasma concentration gradient and forearm blood flow (FBF), was closely related to the circulating RAS. Captopril (0.25, 2.5, 25 mg/100 ml/min per 20 min each dose) unchanged basal FBF in the primary aldosteronism and low renin groups (FBF increase: from 3.9 AE 0.4 to a maximum of 4.1 AE 0.5 and from 3.8 AE 0.3 to a maximum of 4.3 AE 0.5 ml/100 ml/min, respectively), whereas it caused slight vasodilation in the normal renin group (from 3.9 AE 0.3 to a maximum of 5.3 AE 0.7 ml/100 ml/min), and pronounced vasodilation in the high renin group (from 4.0 AE 0.4 to a maximum of 6.4 AE 0.5 ml/100 ml/min). Captopril-induced vasodilation showed a significant direct correlation with the circulating and vascular RAS. The present data, while confirming the existence of a vascular RAS in the forearm of hypertensive patients indicate that the acute vasodilating effect of intrabrachial captopril is linked to a stimulated RAS, either circulating or vascular, supporting the evidence that, in acute conditions, ACE inhibitors exert their vasodilating effect through the RAS blockade.

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Indirect evidence for vascular uptake of circulating renin in hypertensive patients.

Cited by 16 publications

References 22 publications

β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension

β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension

Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients

Relationship between the Circulating and Vascular Renin-Angiotensin System and the Vasodilating Effect of Captopril in Human Hypertension

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