BackgroundTo evaluate the role of kinins in the regulation of cardiovascular function, we studied the phenotype of a mouse strain with disruption of the bradykinin B₂-receptor gene (Bk 2r^−/−).Methods and ResultsUnder basal conditions, tail-cuff blood pressure was higher in Bk2r^−/−than in wild-type Bk2r^+/+and heterozygous Bk2r^+/−mice (124±1 versus 109±1 and 111±2 mm Hg, respectively; P<.01 for both comparisons), a difference that was confirmed by measurements of intra-arterial blood pressure in unanesthetized mice. Heart weight was greater in Bk2r^−/−than in Bk2r^+/+and Bk2r^+/−mice (505±10 versus 449±12 and 477±10 mg/100 g body wt, P<.05). Chronic blockade of B₂-receptors by Icatibant (50 nmol/100 g body wt twice a day SC) or inhibition of nitric oxide synthase by nitro-l-arginine-methyl ester (0.14 mmol/100 g body wt orally) increased the blood pressure of Bk2r^+/+to the levels of Bk2r^−/−mice. Compared with the wild-type strain, both Bk2r^−/−and Bk2r^+/−mice showed exaggerated vasopressor responses to angiotensin II. In addition, chronic administration of an angiotensin AT₁-receptor antagonist reduced the basal blood pressure of Bk2r^−/−by 21±3 mm Hg (P<.05) to the levels of Bk2r^+/+. No difference was detected between strains as far as plasma renin activity and the expression of renin and AT₁-receptor genes are concerned. Chronic salt loading (0.84 mmol/g chow for 15 days) increased the blood pressure of Bk2r^−/−and Bk2r^+/−by 34±3 and 14±6 mm Hg, respectively, whereas it was ineffective in Bk2r^+/+.ConclusionsOur results suggest that a normally functioning B₂-receptor is essential for the maintenance of cardiovascular homeostasis in mice. Dysfunction of the kallikrein-kinin system could contribute to increase blood pressure levels by leaving the activity of vasoconstrictor agents unbalanced.

Antibiotics are used for therapeutic and prophylactic purposes in both human and veterinary medicine and as growth promoting agents in farms and aquaculture. They can accumulate in environmental matrices and in the food chain, causing adverse effects in humans and animals including the development of antibiotic resistance. This review aims to update and discuss the available data on antibiotic residues, using bivalves as biomonitoring organisms. The current research indicates that antibiotics’ presence in bivalves has been investigated along European, American and Asian coasts, with the majority of studies reported for the last. Several classes of antibiotics have been detected, with a higher frequency of detection reported for macrolides, sulfonamides and quinolones. The highest concentration was instead reported for tetracyclines in bivalves collected in the North Adriatic Sea. Only oxytetracycline levels detected in this latter site exceeded the maximum residual limit established by the competent authorities. Moreover, the risk that can be derived from bivalve consumption, calculated considering the highest concentrations of antibiotics residues reported in the analyzed studies, is actually negligible. Nevertheless, further supervisions are needed in order to preserve the environment from antibiotic pollution, prevent the development of antimicrobial resistance and reduce the health risk derived from seafood consumption.

Tissue kallikrein is overexpressed in the kidney of female rats, this sexual dimorphism being associated with a greater effect of early blockade of bradykinin B₂‐receptors on female blood pressure phenotype. We evaluated the effect of ovariectomy and oestradiol benzoate (50 μg kg⁻¹ every two days for two weeks) on the vasodepressor response to intra‐arterial injection of bradykinin (150–900 ng kg⁻¹) and on the expression of bradykinin B₂‐receptors. Ovariectomy reduced the magnitude of the vasodepressor response to bradykinin and unmasked a secondary vasopressor effect. Oestrogen replacement restored the vasodepressor response to bradykinin in ovariectomized rats. The vasodepressor responses to sodium nitroprusside (3–18 μg kg⁻¹), acetylcholine (30–600 ng kg⁻¹), desArg⁹‐bradykinin (150–900 ng kg⁻¹) or prostaglandin E₂ (30–600 ng kg⁻¹) were significantly reduced by ovariectomy. Oestrogen restored to normal the responses to desArg⁹‐bradykinin, acetylcholine and prostaglandin E₂, but not that to sodium nitroprusside. B₂‐receptor mRNA levels were decreased by ovariectomy in the aorta and kidney and they were restored to normal levels by oestrogen. Neither ovariectomy nor oestradiol affected receptor expression in the heart and uterus. These results indicate that oestrogen regulates B₂‐receptor gene expression and function. Since kinins exert a cardiovascular protective action, reduction in their vasodilator activity after menopause might contribute to the increased risk of pathological cardiovascular events. Conversely, the cardioprotective effects of oestrogen replacement might be, at least in part, mediated by activation of the kallikrein‐kinin system. British Journal of Pharmacology (1997) 121, 1763–1769; doi:10.1038/sj.bjp.0701255

The effects of endothelin on regional hemodynamics and renal function were studied in awake normotensive rats. Intravenous injection of endothelin (700 pmol/kg) transiently lowered mean blood pressure (from 108 +/- 2 to 84 +/- 2 mm Hg, p less than 0.01), due to a reduction in total vascular resistance (38 +/- 1%, p less than 0.01), and increased stroke volume (29 +/- 5%, p less than 0.01) and heart rate (from 399 +/- 18 to 447 +/- 18 bpm, p less than 0.05); mesenteric and renal blood flow was reduced (37 +/- 13, p less than 0.05 and 63 +/- 5%, p less than 0.01), whereas carotid blood flow was increased (78 +/- 5%, p less than 0.01). This effect was followed by long-lasting hypertension due to increased total vascular resistance (112 +/- 19%, p less than 0.01); stroke volume, mesenteric, and renal blood flow were reduced (34 +/- 5, 41 +/- 4, and 58 +/- 4%, respectively, p less than 0.05) and carotid blood flow returned to basal levels. Bilateral nephrectomy enhanced the initial hypotensive effect. Pretreatment with nifedipine blocked the hypertensive effect, whereas bilateral nephrectomy did not. A subpressor dose of endothelin (70 pmol/kg) had no effect on stroke volume, mesenteric blood flow, glomerular filtration rate, and plasma renin activity; carotid blood flow was transiently increased (48 +/- 16%, p less than 0.05), then returned to basal levels; renal blood flow decreased (22 +/- 6 and 15 +/- 4% at 30 s and 10 min, respectively p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

1 . The present study was designed to determine if endogenous kinins are involved in the regulation of arterial blood pressure and renal function in conscious rats given deoxycorticosterone enantate (DOC, 25 mg kg⁻¹, s.c., weekly) or vehicle for two weeks. 2 . The bradykinin B₂-receptor antagonist, d-Arg[Hyp³,Thi⁵,d-Tic⁷,Oic⁸]-bradykinin (Hoe 140), at a dose of 300 μg kg⁻¹, s.c., blocked the hypotensive effect of 300 ng kg⁻¹ bradykinin i.a., but it did not alter the blood pressure lowering action of 300 ng kg⁻¹ acetylcholine or prostaglandin E₂. Inhibition of the response to bradykinin persisted up to 6 h after the administration of Hoe 140. 3 . Administration of 300 μg kg⁻¹ Hoe 140 s.c. four times a day did not alter mean blood pressure, renal blood flow, or renal function in rats given DOC-vehicle. However, it decreased urinary volume by 70% (from 48.2 ± 3.8 to 14.3 ± 3.7 ml 24 h⁻¹, P < 0.01) and urinary secretion of sodium by 54% (from 1.02 ± 0.05 to 0.47 ± 0.16 mmol 24 h⁻¹, P < 0.01) and potassium by 30% (from 2.93 ± 0.15 to 2.04 ± 0.15 mmol 24 h⁻¹, P < 0.05) in DOC-treated rats. Mean blood pressure, glomerular filtration rate and total renal blood flow remained unchanged. 4 . Our results suggest that endogenous kinins play a role in the regulation of renal excretion of water and sodium in the presence of elevated levels of DOC.