Impaired effect of relaxin on vasoconstrictor reactivity in spontaneous hypertensive rats

Contains fulltext : 125950.pdf (publisher's version ) (Closed access)Relaxin is thought to be involved in vasodilation to pregnancy by increasing endothelium-dependent vasodilation and compliance, and decreasing myogenic reactivity. Primary (essential) hypertension predisposes to circulatory maladaptation and subsequent gestational hypertensive disease. This study aimed to determine that vascular responses to chronic exposure to relaxin are impaired in young female rats with primary hypertension. In 10-12 weeks old Wistar-Hannover rats (WHR) and spontaneous hypertensive rats (SHR), we determined vascular responses in isolated kidney and mesenteric arteries after 5-days of chronic exposure to relaxin (4 mug/h) or placebo. SHR show decreased sensitivity to phenylephrine (by 67%, p<0.01) and renal perfusion flow (RPFF, by 19%, p<0.01), but no changes in flow-mediated vasodilation, myogenic reactivity or vascular compliance. In WHR, relaxin stimulated flow-mediated vasodilation (2.67 fold, from 48 +/- 9 to 18 +/- 4 mul/min, p = 0.001), inhibited myogenic reactivity (from -1 +/- 2 to 7 +/- 3 mum/10 mmHg, p = 0.01), and decreased sensitivity to phenylephrine (28%, from 1.39 +/- 0.08 to 1.78 +/- 0.10 muM, p<0.01), but left compliance and RPFF unchanged. NO-blockade by L-NAME diminished most relaxin-mediated responses. In SHR, the vasodilator effects of relaxin were blunted for myogenic reactivity and sensitivity to phenylephrine, with similar effects on flow-mediated vasodilation, compliance, RPFF and equal Rxfp1 (relaxin family peptide receptor) gene expression, as compared to WHR. Primary hypertension blunts both the relaxin-induced inhibition of myogenic reactivity and alpha-adrenergic vasoconstrictor response, independent from Rxfp1 gene expression, while the relaxin-dependent enhanced flow-mediated vasodilation remains intact. This implies selective resistance to relaxin in young subjects suffering from primary hypertension

Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments

Abstract not availableRose Crossin, Zane B. Andrews, Natalie A. Sims, Terence Pang, Michael Mathai, Jonathan H. Gooi, Aneta Stefanidis, Brian J. Oldfield, Andrew J. Lawrence, Jhodie R. Dunca

Localization of relaxin receptors in arteries and veins, and region-specific increases in compliance and bradykinin-mediated relaxation after in vivo serelaxin treatment

Relaxin is a potent vasodilator of small resistance arteries and modifies arterial compliance in some systemic vascular beds, yet receptors for relaxin, such as RXFP1, have only been localized to vascular smooth muscle. This study first aimed to localize RXFP1 in rat arteries and veins from different organ beds and determine whether receptors are present in endothelial cells. We then tested the hypothesis that region-specific vascular effects of relaxin may be influenced by the cellular localization of RXFP1 within different blood vessels. The aorta, vena cava, mesenteric artery, and vein had significantly higher (P<0.05) RXFP1 immunostaining in endothelial cells compared with vascular smooth muscle, whereas the femoral artery and vein and small pulmonary arteries had higher (P<0.01) RXFP1 immunostaining in the vascular smooth muscle. Male rats were treated subcutaneously with recombinant human relaxin-2 (serelaxin; 4 μg/h) for 5 d; vasodilation and compliance in mesenteric and femoral arteries and veins were compared with placebo controls. Serelaxin significantly (P=0.04) reduced wall stiffness and increased volume compliance in mesenteric arteries but not in the other vessels examined. This was associated with changes in geometrical properties, and not compositional changes in the extracellular matrix. Serelaxin treatment had no effect on acetylcholine-mediated relaxation but significantly (P<0.001) enhanced bradykinin (BK)-mediated relaxation in mesenteric arteries, involving enhanced nitric oxide but not endothelium-derived hyperpolarization or vasodilatory prostanoids. In conclusion, there is differential distribution of RXFP1 on endothelial and smooth muscle across the vasculature. In rats, mesenteric arteries exhibit the greatest functional response to chronic serelaxin treatment.Maria Jelinic, Chen-Huei Leo, Emiel D. Post Uiterweer, Shaun L. Sandow, Jonathan H. Gooi, Mary E. Wlodek, Kirk P. Conrad, Helena Parkington, Marianne Tare, and Laura J. Parr

International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

Background: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). Objective: We sought to elaborate guidelines for optimizing the management of gynecologic/obstetric events in female patients with HAE-C1-INH. Methods: A roundtable discussion took place at the 6th C1 Inhibitor Deficiency Workshop (May 2009, Budapest, Hungary). A review of related literature in English was performed. Results: Contraception: Estrogens should be avoided. Barrier methods, intrauterine devices, and progestins can be used. Pregnancy: Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid or virally inactivated fresh frozen plasma can be used for long-term prophylaxis if human plasma-derived C1-INH is not available. No safety data are available on icatibant, ecallantide, or recombinant human C1-INH (rhC1INH). Parturition: Complications during vaginal delivery are rare. Prophylaxis before labor and delivery might not be clinically indicated, but pdhC1INH therapeutic doses (20 U/kg) should be available. Nevertheless, each case should be treated based on HAE-C1-INH symptoms during pregnancy and previous labors. pdhC1INH prophylaxis is advised before forceps or vacuum extraction or cesarean section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female patients, genetic counseling, infertility, abortion, lactation, menopause treatment, and endometrial cancer. Conclusions: A consensus for the management of female patients with HAE-C1-INH is presented