RGD Reference Report - RNA silencing targeting PIN (protein inhibitor of neuronal nitric oxide synthase) attenuates the development of hypertension in young spontaneously hypertensive rats.

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RNA silencing targeting PIN (protein inhibitor of neuronal nitric oxide synthase) attenuates the development of hypertension in young spontaneously hypertensive rats.
Authors:	Wang, Su-Chen Lin, Kuan-Miao Chien, Shao-Ju Huang, Li-Tung Hsu, Chien-Ning Tain, You-Lin
Citation:	Wang SC, etal., J Am Soc Hypertens. 2014 Jan;8(1):5-13. doi: 10.1016/j.jash.2013.07.010. Epub 2013 Sep 12.
RGD ID:	13207430
Pubmed:	PMID:24035314 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.jash.2013.07.010 (Journal Full-text)
Nitric oxide (NO) deficiency contributes to hypertension. We previously showed that neuronal nitric oxide synthase (nNOS) was involved in hypertension and kidney damage in spontaneously hypertensive rats (SHRs). The protein inhibitor of nNOS (PIN) has been reported to inhibit activity of nNOS.Thus, we tested whether increased PIN in the kidney results in hypertension and whether small interfering RNA (siRNA) targeting PIN attenuates hypertension in SHRs. Four-week-old male SHRs were assigned into three groups (n = 6-7/group): SHR; SHR + PIN, SHR that received siRNA targeting PIN; and SHR + NC, SHR treated with random negative control siRNA. Rats were sacrificed at 12 weeks of age. PIN protein expression was inhibited considerably when PIN siRNA was transfected into NRK52E cells (90% siRNA at 1 nM). The increases of BP were attenuated by siRNA targeting PIN in 12-week-old SHRs. Immunostaining of nNOS-α and total nNOS was greater in SHR + PIN group than SHR. Moreover, renal superoxide production and 8-hydroxydeoxyguanosine (8-OHdG) staining were more decreased in the SHR + PIN group than SHRs. We conclude that PIN siRNA reduced PIN expression in vitro and in vivo. PIN siRNA therapy attenuates hypertension in SHRs at 12 weeks of age. Our results suggest that PIN is involved in the development of hypertension.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
DYNLL1	Human	hypertension	treatment	ISO	Dynll1 (Rattus norvegicus)		RGD
Dynll1	Rat	hypertension	treatment	IMP			RGD
Dynll1	Mouse	hypertension	treatment	ISO	Dynll1 (Rattus norvegicus)		RGD

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Genes (Rattus norvegicus)

Dynll1 (dynein light chain LC8-type 1)

Genes (Mus musculus)

Dynll1 (dynein light chain LC8-type 1)

Genes (Homo sapiens)

DYNLL1 (dynein light chain LC8-type 1)

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RNA silencing targeting PIN (protein inhibitor of neuronal nitric oxide synthase) attenuates the development of hypertension in young spontaneously hypertensive rats.