Biomedical subjects

Arundhathi Jeyabalan

Publications and source records attributed to Arundhathi Jeyabalan.

9 recordsLinked to original sources

PubMed2007

Renal function during normal pregnancy and preeclampsia.

Glomerular filtration rate and renal plasma flow increase by 40 to 65 and 50 to 85%, respectively, during normal pregnancy in women. Studies using the gravid rat as a model have greatly enhanced our understanding of mechanisms underlying these remarkable changes in the renal circulation during gestation. Hyperfiltration is largely due to increased renal plasma flow, the latter attributable to profound reductions in both the renal afferent and efferent arteriolar resistances. The ovarian hormone, relaxin, mediates renal vasodilation during pregnancy. Relaxin increases vascular gelatinase activity, thereby converting big ET to ET(1-32), which leads to renal vasodilation, hyperfiltration and reduced myogenic reactivity of small renal arteries via the endothelial ET(B) receptor and nitric oxide. Serum concentration of uric acid falls during normal pregnancy as a consequence of increased GFR and/or reduced proximal tubular reabsorption. The elevated urinary excretion of protein during pregnancy is secondary to increased GFR, reduced proximal tubular reabsorption, and perhaps alteration in the electrostatic charge of the glomerular filter. Whether the tubular secretion of Tamm-Horsfall protein increases during normal pregnancy is uncertain. In most women with preeclampsia, renal plasma flow and glomerular filtration rate are at most only modestly decreased as a consequence of increased afferent arteriolar resistance and/or reduced ultrafiltration coefficient. Serum uric acid concentrations are increased mainly as a consequence of reduced renal clearance. Reduced GFR leads to decreased filtered load of uric acid, and plasma volume contraction contributes to increased proximal tubular reabsorption coupled to sodium. The increase in urinary protein excretion in preeclampsia occurs secondary to alterations in the size and/or charge selectivity of the glomerular filter, possible increases in glomerular capillary pressure, and compromise of proximal tubular reabsorption. The renal histologic lesion characteristic of preeclampsia is termed "glomerular endotheliosis". Recent evidence suggests that anti-angiogenic factors emanating from the placenta in preeclampsia contribute to glomerular endotheliosis, proteinuria, and hypertension during disease.

Angiogenic Proteins↗

PubMed2007

Anatomic and functional changes of the upper urinary tract during pregnancy.

An appreciation of the maternal physiologic adaptations that occur in the renal system during pregnancy is fundamental to the understanding and proper clinical management of normal pregnancy, renal disorders in the gravid patient, and pregnancy-specific conditions such as pre-eclampsia. In this article, the authors first address the anatomic changes that occur in the upper urinary tract in normal pregnancy, followed by the dramatic alterations in maternal renal hemodynamics and glomerular filtration. They also briefly discuss renal handling of various substrates in pregnancy, including protein, uric acid, and glucose. An understanding of these changes is important and relevant to the clinician caring for pregnant women.

Female↗

PubMed2006

The effects of cigarette smoking on circulating maternal leukocytes during pregnancy.

During pregnancy, cigarette smoke exposure, a common environmental insult, is damaging to both mother and fetus and is associated with pregnancy loss. The mechanism underlying the pathophysiology of injury is not understood. We hypothesized that smoking during pregnancy interferes with the normal physiological adaptation of the maternal immune system. We used flow cytometry to measure changes in the distribution of subsets of circulating leukocytes and adhesion molecule expression in a prospective cohort of 198 women who had 325 blood samples obtained throughout pregnancy. Smoking status was assessed by plasma cotinine concentration. Smoking increased the frequency of CD3(+) lymphocytes and decreased CD56(+) cells at 14-20 weeks gestation. Smoking also decreased the expression of CD54 on monocytes and CD62L on granulocytes throughout pregnancy. Our data demonstrate that smoking affects several immune parameters, especially early in pregnancy. These perturbations may play a role in pregnancy loss in women who smoke.

Adult↗

PubMed2006

Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin.

UNLABELLED: During pregnancy and chronic relaxin administration to nonpregnant rats (for days), vascular MMP (matrix metalloproteinase)-2 is increased and mediates renal vasodilation, hyperfiltration, and inhibition of myogenic reactivity of small renal arteries. However, the renal vasodilatory actions of relaxin also occur after only several hours of hormone administration to nonpregnant rats, and we hypothesized a pivotal role for vascular MMP-2. Accordingly, we used gelatin zymography, which reveals not only vascular MMP-2, but also MMP-9 activity in small renal arteries isolated from rats administered recombinant human relaxin (rhRLX) or vehicle for 4-6 h. Furthermore, we tested whether myogenic reactivity is inhibited, and if so, whether the inhibition is mediated by increased vascular MMP-2. Surprisingly, we detected no significant difference in either pro or active MMP-2 in small renal arteries isolated from rhRLX and vehicle control treatment groups. In contrast, vascular MMP-9 was up-regulated by 70% (P < 0.0005 vs. vehicle). These results were completely unexpected and novel. MMP-9 protein expression was confined to the vascular smooth muscle. MMP-9, but not MMP-2 activity, was also increased in mesenteric arteries after short-term rhRLX administration (P < 0.005 and >0.05 vs. vehicle, respectively). Myogenic reactivity was inhibited in small renal arteries isolated from nonpregnant rats treated with rhRLX for 4-6 h (P < 0.01 vs. vehicle) and was completely restored by incubation with MMP-9, but not MMP-2 neutralizing antibodies in vitro. CONCLUSION: In contrast to chronic rhRLX administration, MMP-9 rather than MMP-2 plays a central role in the vasodilatory effect of short-term relaxin administration.

Animals↗

PubMed2006

Matrix metalloproteinase-2 activity, protein, mRNA, and tissue inhibitors in small arteries from pregnant and relaxin-treated nonpregnant rats.

Vascular gelatinase activity is essential for pregnancy- and relaxin (Rlx)-induced renal vasodilation and hyperfiltration in rats. The objective of this study was to further elucidate the mechanisms for the increase in vascular matrix metalloproteinase (MMP)-2 activity caused by pregnancy and Rlx. We first corroborated our earlier work by showing that pro- and active forms of MMP-2 were increased in small renal arteries from pregnant compared with virgin rats and Rlx-treated compared with vehicle-treated nonpregnant rats. We next investigated other artery types and showed that MMP-2 activity was upregulated in mesenteric arteries from pregnant rats (pro-MMP-2 by 50% and active MMP-2 by 40%, both P<0.05) and from Rlx-treated nonpregnant rats (pro-MMP-2 by 50% and active MMP-2 by 90%, both P<0.005) compared with their respective controls. To corroborate these results obtained by gelatin zymography, pro-MMP-2 protein was determined by Western analysis in the same small arteries. Pro-MMP-2 protein was increased in small renal arteries from pregnant compared with virgin rats and from Rlx- compared with vehicle-treated nonpregnant rats: pro-MMP-2-to-beta-actin ratio=0.29 vs. 0.21 (P<0.01) and 0.43 vs. 0.32 (P<0.005). Findings were similar for mesenteric arteries. MMP-2 mRNA as measured by real-time PCR was increased in small renal arteries from pregnant and Rlx-treated nonpregnant rats compared with their respective controls. There were no significant differences in tissue inhibitor of metalloproteinase (TIMP-1 or TIMP-2) activity by reverse zymography in small renal arteries. Thus increases in MMP-2 mRNA and protein expression are major factors contributing to increased MMP-2 activity in small arteries from pregnant and Rlx-treated nonpregnant rats.

Animals↗

PubMed2005

Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats.

Chronic administration of recombinant human relaxin (rhRLX) to conscious, normotensive rats (male and female) increases cardiac output (CO) and global arterial compliance (ACg) and reduces systemic vascular resistance (SVR) with no change in mean arterial pressure (MAP). Effects (magnitude and temporal pattern) of relaxin on systemic hemodynamics and arterial properties in hypertensive animal models are not known. Accordingly, the major goal of the present study was to determine the cardiovascular effects of rhRLX in hypertensive rats using 2 models: Long-Evans rats chronically administered angiotensin II (AII) and spontaneously hypertensive rats (SHR). CO and systemic arterial load, as quantified by SVR and ACg, were obtained using methods reported previously by us. In rats with AII-induced hypertension, acute rhRLX administration (up to 6 hours) significantly increased CO and ACg (24.9+/-3.9 and 34.3+/-12.6% above baseline, respectively) and significantly decreased SVR (17.2+/-3.5%) without changing MAP. In contrast, acute rhRLX administration to SHR and normotensive rats for up to 6 hours failed to produce any significant changes in CO, ACg, SVR, or MAP. However, chronic rhRLX administration (1 to 7 days) to SHR yielded significant changes (24.0+/-8.1 and 22.3+/-6.6% increases in CO and ACg, respectively, and a 13.3+/-5.3% decrease in SVR, with no change in MAP). In conclusion, rhRLX increases CO and reduces arterial load in hypertensive rats without reducing MAP. However, the time course of response to rhRLX treatment is dependent on the model of hypertension such that rats characterized by AII-mediated hypertension responded more rapidly to rhRLX administration than SHR.

Angiotensin II↗

PubMed2005

Vaginal breech deliveries selected using computed tomographic pelvimetry may be associated with fewer adverse outcomes.

OBJECTIVE: Vaginal breech (VB) delivery at term remains controversial. Our objective was to compare neonatal and maternal outcomes in VB deliveries selected using computed tomographic (CT) pelvimetry to those selected clinically. METHODS: A retrospective cohort study of singleton, term, VB deliveries with adequate clinical pelvimetry and estimated fetal weight of 3,850 g was performed. Women in the CT group had adequate pelvimetry by CT measurements. Neonatal and maternal outcomes were recorded. RESULTS: Of the VB deliveries, 58 women had adequate CT pelvimetry and 37 women were selected using clinical criteria alone. There were no perinatal deaths. Neonatal morbidity was significantly lower in VB deliveries selected using CT criteria at 0% versus 10.8% in the clinically selected group (p=0.02). CONCLUSION: VB deliveries selected using CT pelvimetry may be associated with fewer adverse neonatal outcomes than those selected using only clinical criteria. Therefore, it is inappropriate, without CT pelvimetry and strict selection criteria, to conclude that VB deliveries are unsafe. Our experience suggests that there may be a population in which VB delivery is a safe alternative if selected using a combination of specific clinical, sonographic, and CT criteria.

Adolescent↗

PubMed2005

Acute renal failure in pregnancy.

OBJECTIVES: To provide an evidence-based, up-to-date review of the literature regarding the assessment and management of acute renal failure that may affect women during pregnancy and the postpartum period. DESIGN: A review of the current literature was performed. RESULTS: Acute renal failure is a rare complication of pregnancy but is associated with significant morbidity and mortality. Management requires knowledge of the renal physiologic changes occurring in pregnancy and the relevant diagnoses, both pregnancy-specific and those that may coincidentally occur with pregnancy. In addition, fetal effects must be taken into consideration. CONCLUSIONS: Ideal care for women with acute renal failure in pregnancy or postpartum requires a multidisciplinary approach that may include maternal-fetal medicine, critical care medicine, nephrology, and neonatology specialists.

Acid-Base Equilibrium↗

PubMed2003

Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries.

During pregnancy, relaxin stimulates nitric oxide (NO)-dependent renal vasodilation, hyperfiltration and reduced myogenic reactivity of small renal arteries via the endothelial ETB receptor subtype. Our objective in this study was to elucidate the mechanisms by which relaxin stimulates the endothelial ETB receptor/NO vasodilatory pathway. Using chronically instrumented conscious rats, we demonstrated that a specific peptide inhibitor of the gelatinases MMP-2 and -9, cyclic CTTHWGFTLC (cyclic CTT), but not the control peptide, STTHWGFTLS (STT), completely reversed renal vasodilation and hyperfiltration in relaxin-treated rats. Comparable findings were observed with a structurally different and well-established, general antagonist of MMPs, GM6001. In contrast, phosphoramidon, an inhibitor of endothelin-converting enzyme, did not significantly change the renal vasodilatory response to relaxin administration. When small renal arteries were incubated with either of the general MMP inhibitors, GM6001 or TIMP-2 (tissue inhibitor of MMP), or with the specific gelatinase inhibitor, cyclic CTT, the reduced myogenic reactivity of these blood vessels from relaxin-treated nonpregnant and midterm pregnant rats was totally abolished. Moreover, a neutralizing antibody specific for MMP-2 completely abrogated the reduced myogenic reactivity of small renal arteries from relaxin-treated nonpregnant and midterm pregnant rats. In contrast, phosphoramidon did not significantly affect the reduction in myogenic reactivity. Using gelatin zymography, we showed increased pro and active MMP-2 activity in small renal arteries from relaxin-treated nonpregnant and midterm pregnant rats relative to the control animals. Thus, inhibitors of MMPs in general and of gelatinases in particular reverse the renal vascular changes induced by pregnancy or relaxin administration to nonpregnant rats. Finally, the typical reduction in myogenic reactivity of small renal arteries from relaxin-treated nonpregnant rats was absent in ETB receptor-deficient rats, despite an increase in vascular MMP-2 activity. These results indicate an essential role for vascular gelatinase, which is in series with, and upstream of, the endothelial ETB receptor/NO signaling pathway in the renal vasodilatory response to relaxin and pregnancy.

Animals↗