Recent studies suggest that superoxide production by the NADPH/NADH oxidase may be involved in smooth muscle cell growth and the pathogenesis of hypertension. We previously showed that angiotensin II (Ang II) activates a p22phoxbased NADPH/NADH oxidase in cultured rat vascular smooth muscle cells and in animals made hypertensive by infusion of Ang II. To investigate the mechanism responsible for this increased oxidase activity, we examined p22phox mRNA expression in rats made hypertensive by implanting an osmotic minipump that delivered Ang II (0.7 mg/kg per day). Blood pressure began to increase 3 days after the start of Ang II infusion and remained elevated for up to 14 days. Expression of p22phox mRNA in aorta was also increased after 3 days and reached a maximum increase of 338 +/- 41% by 5 days after pump implantation compared with the value after sham operation. This increase in mRNA expression was accompanied by an increase in the content of the corresponding cytochrome (twofold) and NADPH oxidase activity (179 +/- 11% of that in sham-operated rats 5 days after pump implantation). Treatment with the antihypertensive agents losartan (25 mg/kg per day) or hydralazine (15 mg/kg per day) inhibited this upregulation of mRNA levels and activity. Furthermore, infusion of recombinant heparin-binding superoxide dismutase decreased both blood pressure and p22phox mRNA expression. In situ hybridization of aortic tissue showed that p22phox mRNA was expressed in medial smooth muscle as well as in the adventitia. These findings suggest that Ang II-induced hypertension activates the NADPH/NADH oxidase system by upregulating mRNA levels of one or several components of this oxidase system, including the p22phox, and that the NADPH/NADH oxidase system is associated with the pathology of hypertension in vivo.

Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation.

Future directions include preceding and following the IAT with more robust reflection and education on unconscious bias. The authors join others in calling for an examination of bias at all levels of academic medicine.

Monocyte chemoattractant protein-1 (MCP-1), a potent monocyte chemoattractant synthesized by vascular cells and monocytes, has been proposed to be an important mediator of inflammatory responses in the arterial vasculature. It was recently demonstrated that hypertension is associated with an inflammatory response in the arterial wall. To determine the effect of hypertension on arterial MCP-1 expression, we induced hypertension in Sprague-Dawley rats by infusing angiotensin II (0.75 mg x kg[-1] x d[-1] SC) for 7 days. Using Northern blot analysis, we detected a 3.6-fold increase in MCP-1 mRNA in the aortas of hypertensive rats. When we normalized blood pressure in angiotensin II-treated rats through oral administration of the nonspecific vasodilator hydralazine (15 mg x kg[-1] x d[-1]), aortic MCP-1 mRNA expression was significantly reduced. Similar results were obtained with a norepinephrine model of hypertension. Taken together, these data suggest that mechanical factors may be responsible in part for the upregulation of expression. Consistent with this interpretation, we found that cultured rat aortic vascular smooth muscle cells exposed to mechanical strain (20% peak deformation at 1 Hz) exhibited a marked increase in MCP-1 expression, suggesting the hemodynamic strain imparted onto arterial cells in hypertension is an important stimulus underlying this phenomenon. These results provide important insights into the in vivo regulation of MCP-1 and have potential implications for understanding the influence of hypertension on atherosclerosis.

In an attempt to help us navigate a complex world, our unconscious minds make certain group associations on the basis of our experiences. Physicians are not immune to these implicit associations or biases, which can lead physicians to unknowingly associate certain demographic groups with negative concepts, like danger, noncompliance, and lower competence. These biases can influence clinical decision making in ways that potentially harm patients and may unfairly influence the medical school, residency, and fellowship application processes for candidates in certain underrepresented groups. To minimize the potential negative impact of implicit biases on patient care and diversity in the medical profession, physician-leaders have a responsibility to understand biases and how to consciously override them. This article discusses the potential impact of implicit bias in health care and student/trainee selection and reviews research-proven tools to reduce implicit bias in one-on-one interactions.

The relative lack of diversity in medicine is a rate limiting factor in efforts to eliminate health care disparities. Many medical schools struggle to matriculate student bodies that reflect the diversity of this country. Actively recruiting is one tactic to diversify a medical school's applicant pool, but in isolation is not enough. Our medical school admissions committee made a number of programmatic changes that contributed to our current compositional diversity that may be instructive to others. This report from the field on the experience of one U.S. medical school describes several admissions committee initiatives that can be undertaken to increase the yield of students from groups underrepresented in medicine who matriculate to medical school.

Background A large volume of literature has documented racial disparities in the delivery of cardiovascular care in the United States and that decreased access to procedures and undertreatment lead to worse outcomes. A lack of diversity among physicians is considered to be a major contributor. The fellowship training program in cardiovascular medicine at The Ohio State University Medical Center had never trained a fellow from a minority group underrepresented in medicine (URM) before 2007. Intervention In 2005, the fellowship made it a priority to recruit and match URM candidates in an effort to address the community's lack of diversity and disparities in cardiovascular care. Methods Program leaders revised the recruitment process, making diversity a high priority. Faculty met with members of diverse residency programs during visits to other institutions, the focus of interview day was changed to highlight mentorship, additional targeted postinterview communications reached out to highly competitive applicants, and a regular mentoring program was constructed to allow meaningful interaction with URM faculty and fellows. Results Since these changes were implemented, the program has successfully matched a URM fellow for 5 consecutive years. Such candidates currently make up 4 of 16 total trainees (25%) in the fellowship in cardiovascular medicine. Conclusions The cardiovascular medicine fellowship training program at The Ohio State University was able to revise recruitment to attract competitive URM applicants as part of a concerted effort. Other educational programs facing similar challenges may be able to learn from the university's experiences.

Thrombin has been implicated as an important mediator of vascular lesion formation in atherosclerosis and restenosis. To investigate a potential role for thrombin signaling in the vascular response to hypertension, we have studied thrombin receptor (TR) expression and regulation in hypertensive rats. Aortic TR mRNA was upregulated by angiotensin II (Ang II)–induced hypertension (10.7±2.5 times control, P <.02), which correlated with a 4-fold increase in thrombin-induced constriction in isolated endothelium-denuded aortic rings. The AT 1 receptor antagonist losartan normalized blood pressure and TR mRNA. Conversely, lowering blood pressure to the same degree with hydralazine did not abolish the upregulation of TR mRNA expression. When low-renin low–Ang II hypertension was induced in Dahl salt-sensitive rats, there was no detectable increase in the expression of aortic thrombin receptor mRNA. Finally, treatment with a chimeric heparin-binding form of the recombinant human Cu/Zn superoxide dismutase caused complete inhibition of TR mRNA upregulation, suggesting that an increased rate of superoxide anion production is an important signaling mechanism. Thus, increased TR expression via a redox-sensitive mechanism in the aortic smooth muscle of rats treated with Ang II represents a novel in vivo mechanism through which the hypertensive effects of Ang II are mediated.