Chronic low-dose angiotensin II (Ang II) infusion for 13 days mimics two-kidney, one clip Goldblatt hypertension and increase intrarenal Ang II levels. We performed studies to determine the time course for the enhancement of intrarenal Ang II levels and whether the increased intrarenal Ang II is a tissue-specific event and requires a receptor-mediated step. Male Sprague-Dawley rats were uninephrectomized, and either vehicle or Ang II (40 ng/min) was infused via a subcutaneous osmotic minipump. Plasma and renal Ang II levels were measured 3, 7, 10, and 13 days after minipump implantation. Compared with controls (126 +/- 2 mm Hg), systolic pressure in Ang II-infused rats exhibited a detectable increase by day 6 (146 +/- 2 mm Hg) and continued to increase to 189 +/- 5 mm Hg by day 12. Plasma Ang II levels were elevated by day 3, whereas intrarenal Ang II levels were not significantly elevated until 10 days of Ang II infusion. Renal injury characterized by focal and segmental glomerulosclerosis was evident after 13 days of Ang II infusion. Losartan (30 mg/kg per day) prevented the development of hypertension in the Ang II-infused rats for the duration of the infusion period (125 +/- 1 mm Hg) and reduced the degree of glomerular injury. Plasma renin activity was suppressed in the Ang II-infused group but was elevated markedly in both losartan-treated groups. Plasma Ang II levels were elevated in the Ang II-infused rats and were even higher during losartan treatment. Intrarenal Ang II levels were enhanced significantly (354 +/- 60 versus 164 +/- 23 fmol/g) in the Ang II-infused rats. However, losartan treatment prevented the augmentation of intrarenal Ang II caused by Ang II infusion. Heart and adrenal Ang II levels were not significantly increased in the Ang II-infused rats but were significantly elevated during losartan treatment. These results suggest that the tissue-specific elevations of intrarenal Ang II levels caused by chronic Ang II infusion are mediated by angiotensin type 1 receptor activation, which leads to either receptor-mediated internalization of Ang II, enhancement of intrarenal Ang II formation, or both.

Background An outbreak of coronavirus disease 2019 (Covid-19) occurred on the U.S.S. Theodore Roosevelt , a nuclear-powered aircraft carrier with a crew of 4779 personnel. Methods We obtained clinical and demographic data for all crew members, including results of testing by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). All crew members were followed up for a minimum of 10 weeks, regardless of test results or the absence of symptoms. Results The crew was predominantly young (mean age, 27 years) and was in general good health, meeting U.S. Navy standards for sea duty. Over the course of the outbreak, 1271 crew members (26.6% of the crew) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by rRT-PCR testing, and more than 1000 infections were identified within 5 weeks after the first laboratory-confirmed infection. An additional 60 crew members had suspected Covid-19 (i.e., illness that met Council of State and Territorial Epidemiologists clinical criteria for Covid-19 without a positive test result). Among the crew members with laboratory-confirmed infection, 76.9% (978 of 1271) had no symptoms at the time that they tested positive and 55.0% had symptoms develop at any time during the clinical course. Among the 1331 crew members with suspected or confirmed Covid-19, 23 (1.7%) were hospitalized, 4 (0.3%) received intensive care, and 1 died. Crew members who worked in confined spaces appeared more likely to become infected. Conclusions SARS-CoV-2 spread quickly among the crew of the U.S.S. Theodore Roosevelt . Transmission was facilitated by close-quarters conditions and by asymptomatic and presymptomatic infected crew members. Nearly half of those who tested positive for the virus never had symptoms.

The objective of this study was to investigate the singular role of elevated angiotensin II (ANG II) levels in the development of two-kidney, one-clip (2K1C) Goldblatt hypertension in the rat and specifically in the altered intrarenal ANG II levels that occur in the nonclipped kidney. As a substitute for the clipped kidney, chronic delivery of ANG II (40 ng/min) via an osmotic minipump implanted subcutaneously was used to mimic plasma ANG II levels observed in 2K1C rats during the developmental phase of hypertension. Arterial pressure increased gradually over a period of 14 days, and a pressure profile similar in magnitude and temporal pattern to that of the 2K1C rats was observed. Systemic ANG II was elevated to similar levels in the 2K1C (60 +/- 13 fmol/ml) and ANG II-infused rats (72 +/- 15 fmol/ml) compared with intact two-kidney control animals (31 +/- 6 fmol/ml; P < 0.05) or uninephrectomized rats (13 +/- 1 fmol/ml; P < 0.05). Although renin content was markedly suppressed (80%), intrarenal ANG II content of the contralateral kidneys of the 2K1C groups (86 +/- 12 fmol/g) and the ANG II-infused group (150 +/- 17 fmol/g) was greater than that of the two-kidney control (53 +/- 7 fmol/g; P < 0.05) and uninephrectomized control animals (42 +/- 5 fmol/g; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies have shown that chronic lowdose administration of 40 ng/min angiotensin II by osmotic minipump to uninephrectomized rats mimics the temporal hypertensive response and the circulating angiotensin II levels observed in two-kidney, one clip Goldblatt rats. Furthermore, renal tissue angiotensin II contents were higher than the circulating angiotensin II levels, suggesting that circulating angiotensin II induces endogenous intrarenal angiotensin II production. The present study examined the molecular mechanisms by which intrarenal angiotensin II production is modulated in angiotensin H-induced and two-kidney Goldblatt hypertension. Two weeks after clipping, intrarenal renin mRNA levels were elevated threefold in the clipped kidney of Goldblatt rats but were markedly suppressed in the nonclipped kidneys of Goldblatt rats (28% of control values) and in the remaining kidney of uninephrectomized angiotensin II-infused rats (7% of control values). In contrast, there were sustained levels of angiotensinogen mRNA in the kidneys and livers of Goldblatt and angiotensin II-infused rats, indicating differential regulation of the genes of the renin-angiotensin system. Renal kallikrein gene expression was not altered in either of the hypertensive groups 14 days after the induction of hypertension, suggesting the absence of an enhanced counteracting kinin influence.

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