Age dependent expression and distribution of nitric oxide (NO) synthase isoforms in the ovine kidney

Abstract

<span style="font-size:10pt;">The aim of the present study was to measure intrarenal spatial and temporal localization of all three nitric oxide synthase (NOS) isoforms in the developing ovine kidney. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western Blot analyses, and <i>in situ </i>hybridization techniques were performed for NOS I -III isoforms in renal tissue obtained from sheep aged ~24 h, one, three, six, and 12 weeks post natally (N = 3). </span><span style="font-size:10pt;">RT-PCR performed on cortical and medullary kidney tissue revealed the presence of all three NOS isoforms from day one to 12 weeks postnatally. </span><span style="font-size:10pt;">NOS I and NOS II mRNA levels were greater in cortex compared to medulla during the first three weeks whereas NOS III mRNA levels were predominantly transcribed within the medulla. In all NOS isoforms, there was a decrease in cortical mRNA levels after three to six weeks. Protein levels confirmed the presence of all three NOS isoforms over the first three months of postnatal life. By demonstrating NOS isoform transcripts to be more abundant in the early post natal period, these findings may provide insight into the age dependent role of NO in modulating kidney function during ontogeny.</span

Renal Nitric Oxide Deficiency and Chronic Kidney Disease in Young Sheep Born with a Solitary Functioning Kidney

“…In support of this, nNOS makes a greater contribution to the control of RBF in the postnatal period but in the adult pig, eNOS contributes predominantly 10 . In the sheep kidney, all three isoforms of NOS have the greatest expression at birth, particularly in the renal cortex and the levels start to decline from 12 weeks of age 34 , providing strong evidence that NO plays an important role in the regulation of renal function in the early postnatal period 17 . Thus, NO deficiency may drive the development of hypertension and renal dysfunction when renal mass is reduced early in life, as a result of being born with a SFK or low nephron number.…”

“…Thus the kidney of uni-x sheep, due to the inability to recruit NO, may have an impaired ability to regulate net glomerular filtration pressure, and thus GFR, in response to changes in perfusion pressure. In the kidney, NO is produced by endothelial NOS (eNOS) in the vasculature and neuronal NOS (nNOS) in the macula densa cells, which acts to modulate segmental renal vascular resistance and glomerular dynamics 34 10 . Additionally, whilst urine flow decreased by a similar extent in both groups, the reduction in sodium excretion was attenuated in the uni-x (48%) as compared to the sham lambs (76%) in response to L-NAME.…”

Angiotensin receptors modulate the renal hemodynamic effects of nitric oxide in conscious newborn lambs

“…In all NOS isoforms, there was a decrease in cortical mRNA levels after 3–6 weeks of postnatal life (Davis et al. ).…”

Participação do óxido nítrico na fisiopatologia da doença renal crônica

“…A isoforma eNOS, rotineiramente denominada de isoforma III, está ligada à membrana das células endoteliais, bem como a adesão e agregação plaquetária. A eNOS pode ser encontrada em sinciciotrofoblastos, células epiteliais tubulares do rim, células intersticiais do cólon e hipocampo (MONCADA; PALMER; HIGGS, 1991;DAVIS et al, 2013).…”

“…Essa isoforma pode ser expressa em uma grande variedade dos tipos celulares, incluindo macrófagos, linfócitos, neutrófilos, eosinófilos, células de Kupffer, hepatócitos e células endoteliais e são independentes de íons de cálcio para sua ativação. Uma das grandes diferenças entre a NOS constitutiva e a induzível é que a iNOS é capaz de liberar grandes quantidades de NO por períodos prolongados, podendo produzir efeitos exagerados, resultando em respostas tóxicas ao organismo, enquanto que a cNOS produz pequenas quantidades de NO e por um menor tempo (DAVIS et al, 2013).…”