Myogenic reactivity is reduced in small renal arteries  isolated from relaxin-treated rats

Novak, Jacqueline; Ramirez, Rolando; Gandley, Robin E.; Sherwood, O. D.; Conrad, Kirk P.

doi:10.1152/ajpregu.00635.2001

Cited by 109 publications

(159 citation statements)

References 23 publications

(45 reference statements)

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“…On the one hand, the expected attenuation of myogenic constriction was not observed in small renal arteries isolated from ET B receptor-deficient rats that were either pregnant or nonpregnant and chronically administered rhRLX, thus corroborating earlier findings using the ET B receptor antagonists RES-701-1 and SB209670 (37,44,51,56,60). On the other hand, enhanced MMP-2 activity was observed in small renal arteries isolated from the same rats.…”

Section: Molecular Mechanisms Of Relaxin Vasodilation: Sustained Vasosupporting

confidence: 86%

“…As a consequence of the reduced renal vascular resistance, both RPF and GFR also increased by ϳ25%. In association with renal vasodilation, myogenic constriction of small renal arteries isolated from the relaxin-treated rats was attenuated, thus mimicking the reduced myogenic constriction observed in small renal arteries from midterm pregnant rats (37,60). Analogous to both midterm and late pregnancy in rats (12,19,61), the renal pressor response to an acute intravenous infusion of angiotensin II was attenuated in nonpregnant rats that were chronically administered relaxin (22).…”

Section: Relaxin Administration Mimics Maternal Vasodilation Of Pregnmentioning

confidence: 77%

“…In analogous studies, results using the mixed ET A/B antagonist SB209670 supported these findings (15). Subsequent investigations further demonstrated that the ET B receptor and NO mediate renal vasdilation and hyperfiltration in conscious nonpregnant rats administered rhRLX for 5 days, and the same molecular intermediates also underlie the attenuation of myogenic constriction in small renal arteries isolated from midterm pregnant and relaxin-infused nonpregnant rats (21,22,37,60). Although the data are limited, there is no evidence for upregulation of endothelial NOS in the major zones of the kidney, in isolated small renal arteries or renal microvasculature of midterm pregnant rats, nor in the renal cortex of relaxin-treated nonpregnant rats (1,59).…”

Section: Molecular Mechanisms Of Relaxin Vasodilation: Sustained Vasomentioning

confidence: 86%

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Maternal vasodilation in pregnancy: the emerging role of relaxin

Conrad

2011

American Journal of Physiology-Regulatory, Integrative and Comp

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180

141

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Conrad KP. Maternal vasodilation in pregnancy: the emerging role of relaxin. Am J Physiol Regul Integr Comp Physiol 301: R267-R275, 2011. First published May 25, 2011 doi:10.1152/ajpregu.00156.2011.-Pregnancy is a unique physiological condition of profound maternal renal and systemic vasodilation. Our goal has been to unveil the reproductive hormones mediating this remarkable vasodilatory state and the underlying molecular mechanisms. In addition to advancing our knowledge of pregnancy physiology, reaching this goal may translate into therapeutics for pregnancy pathologies such as preeclampsia and for diseases associated with vasoconstriction and arterial stiffness in nonpregnant women and men. An emerging player is the 6 kDa corpus luteal hormone relaxin, which circulates during pregnancy. Relaxin administration to rats and humans induces systemic and renal vasodilation regardless of sex, thus mimicking the pregnant condition. Immunoneutralization or elimination of the source of circulating relaxin prevents renal and systemic vasodilation in midterm pregnant rats. Infertile women who become pregnant by donor eggs (IVF with embryo transfer) lack a corpus luteum and circulating relaxin, and they show a markedly subdued gestational increase in glomerular filtration rate. These data implicate relaxin as one of the vasodilatory reproductive hormones of pregnancy. There are different molecular mechanisms underlying the so-called rapid and sustained vasodilatory actions of relaxin. The former is mediated by G␣ i/o protein coupling to phosphatidylinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of endothelial nitric oxide synthase, the latter by vascular endothelial and placental growth factors, and increases in arterial gelatinase(s) activity. The gelatinases, in turn, hydrolyze big endothelin (ET) at a gly-leu bond to form ET 1-32, which activates the endothelial ET B receptor/nitric oxide vasodilatory pathway.

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Section: Molecular Mechanisms Of Relaxin Vasodilation: Sustained Vasosupporting

confidence: 86%

Section: Relaxin Administration Mimics Maternal Vasodilation Of Pregnmentioning

confidence: 77%

Section: Molecular Mechanisms Of Relaxin Vasodilation: Sustained Vasomentioning

confidence: 86%

See 1 more Smart Citation

Maternal vasodilation in pregnancy: the emerging role of relaxin

Conrad

2011

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

180

141

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“…Previous reports have indicated that relaxin simulates NOmediated responses in multiple vascular and non-vascular tissues , Novak et al 2002, Failli et al 2005, McGuane et al 2011, van Drongelen 2011. Our data show that TA and Branch arterioles dilate to the same extent relaxin, once the maximum size of the vessels is taken into account; however, MI arterioles do not respond directly to relaxin.…”

Section: Different Microvascular Responses To Relaxinsupporting

confidence: 49%

Relaxin induces rapid, transient vasodilation in the microcirculation of hamster skeletal muscle

Willcox¹,

Summerlee²,

Murrant³

2013

Journal of Endocrinology

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Relaxin produces a sustained decrease in total peripheral resistance, but the effects of relaxin on skeletal muscle arterioles, an important contributor to systemic resistance, are unknown. Using the intact, blood-perfused hamster cremaster muscle preparation in situ, we tested the effects of relaxin on skeletal muscle arteriolar microvasculature by applying 10 K10 M relaxin to second-, third-and fourth-order arterioles and capillaries. The mechanisms responsible for relaxin-induced dilations were explored by applying 10 K10 M relaxin to second-order arterioles in the presence of 10K3 M tetraethylammonium (TEA) or 10 K7 M iberiotoxin (IBTX, calcium-associated K C channel inhibitor). Relaxin caused second-(peak change in diameter: 8.3G1.7 mm) and third (4.5G1.1 mm)-order arterioles to vasodilate transiently while fourth-order arterioles did not (0.01G0.04 mm). Relaxin-induced vasodilations were significantly inhibited by L-NAME, GLIB, TEA and IBTX. Relaxin stimulated capillaries to induce a vasodilation in upstream fourth-order arterioles (2.1G0.3 mm), indicating that relaxin can induce conducted responses vasodilation that travels through blood vessel walls via gap junctions. We confirmed gap junction involvement by showing that gap junction uncouplers (18-b-glycyrrhetinic acid (40!10 K6 M) or 0.07% halothane) inhibited upstream vasodilations to localised relaxin stimulation of second-order arterioles. Therefore, relaxin produces transient NO-and K C channel-dependent vasodilations in skeletal muscle arterioles and stimulates capillaries to initiate conducted responses. The transient nature of the arteriolar dilation brings into question the role of skeletal muscle vascular beds in generating the sustained systemic haemodynamic effects induced by relaxin.

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“…Relaxin administration to nonpregnant female rats also diminishes the renal vasoconstrictor response to angiotensin II, similar to the dampening influence of rat gestation (25,27,28). Moreover, reduced myogenic reactivity of small renal arteries is observed after relaxin administration, analogous to vessels isolated from midterm pregnant rats (29,30). Finally, relaxinneutralizing antibodies or removal of circulating relaxin by ovariectomy completely abolishes the renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small renal arteries, as well as the osmoregulatory changes in midterm pregnant rats (31).…”

Section: Newer Aspects On Relaxin In Pregnancy and Preeclampsiamentioning

confidence: 73%

New Aspects in the Pathophysiology of Preeclampsia

Davison¹,

Homuth²,

Jeyabalan³

et al. 2004

Journal of the American Society of Nephrology

171

109

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Abstract. Preeclampsia, the de novo occurrence of hypertension and proteinuria after the 20th week of gestation, continues to exert an inordinate toll on mothers and children alike. Recent clinical trials, new physiologic insights, and novel observations on pathogenesis have altered the thinking about preeclampsia. The mechanisms surrounding relaxin and its effects on the circulation and on matrix metalloproteinases have been elucidated. The growth factor's receptor, fms-like tyrosine kinase 1, has been shown to exist in a soluble form that is able to inactivate vascular endothelial-derived growth factor and human placental growth factor. Compelling evidence has been brought forth suggesting that fms-like tyrosine kinase 1 is a circulating factor that can cause preeclampsia. Preeclamptic women have high circulating levels of asymmetric dimethyl arginine that could account for the generalized endothelial dysfunction observed in preeclampsia. Preeclamptic women also produce novel autoantibodies that may serve to activate angiotensin receptors. These new observations raise the possibility that the treatment of preeclamptic women will soon be improved.The term preeclampsia refers to the new onset of hypertension (Ͼ140/90 mmHg) and proteinuria after 20 wk of gestation in previously normotensive, nonproteinuric women (1). The condition is common and occurs in~5% of pregnancies in the United States and Europe. Eclampsia is a life-threatening complication and is characterized by grand mal seizures. The term comes from the Greek word for lightning. A severe variant of preeclampsia also features hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). This condition occurs iñ 1 per 1000 pregnancies. Predisposing factors are a positive family history, hypertension, diabetes, preexisting renal disease, multiple pregnancies, and a poor obstetric history. Nephrologists are often called on to see preeclamptic women because of the severe BP elevation and renal disease. Thus, new clinical or experimental information on this condition is important information for nephrologists. Preeclampsia and Subsequent Cardiovascular RiskThe relevance of preeclampsia to the offspring is well recognized. Children who are born to preeclamptic mothers commonly have low birth weight, and their subsequent cardiovascular risk has been a vast investigational field. The mother's outcome has attracted less interest. Chesley, the father of modern preeclampsia research, was of the opinion that once the condition was over, the mothers had no greater risk of adverse long-term outcomes than women without preeclampsia from the general population (2). This issue may prove to be the only matter in which Chesley's opinion was erroneous. Several recent studies suggest that the converse is the case. Smith et al. (3) studied the pregnancy complications and the maternal risk of ischemic cardiac death in 129,290 births. They found that delivering an infant with low birth weight for gestational age increased the hazard ratio for ischemic heart disease o...

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Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats

Cited by 109 publications

References 23 publications

Maternal vasodilation in pregnancy: the emerging role of relaxin

Maternal vasodilation in pregnancy: the emerging role of relaxin

Relaxin induces rapid, transient vasodilation in the microcirculation of hamster skeletal muscle

New Aspects in the Pathophysiology of Preeclampsia

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