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Background: Guidelines recommend lowering systolic blood pressure below 130 mm Hg, irrespective of previous strokes. However, there is a concern that lowering systolic blood pressure in people with low baseline diastolic blood pressure might increase the risk of stroke. Methods: We conducted a secondary analysis of the Secondary Prevention of Small Subcortical Strokes trial that randomly assigned participants with a history of subcortical strokes to an intensive ( Results: Mean baseline systolic and diastolic blood pressures were 143±19 and 78±11 mm Hg, respectively. Within each baseline diastolic blood pressure tertile, the achieved diastolic was lower in the intensive versus standard arm. There were 275 stroke events over 10 889 years of follow-up. Lower baseline diastolic blood pressure was associated with increased risk of stroke in an observational spline regression model. Hazard ratios relating blood pressure intervention with the risk of stroke in the lowest (hazard ratio, 0.78 [95% CI, 0.52–1.16]) and the highest (hazard ratio, 0.80 [95% CI, 0.53–1.21]) baseline diastolic tertiles were similar ( P =0.95). Results were similar for the cardiovascular composite. Conclusions: Intensive systolic control does not appear to increase the risk of stroke in those with low baseline diastolic blood pressure and prior stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00059306.

The renal tubular (pro)renin receptor (PRR) has been shown to modulate water balance, blood pressure and Na + homeostasis. We recently reported that inducible nephron wide deletion of the PRR results in Na + wasting, reduced epithelial Na + channel (ENaC) expression in the kidney and attenuated hypertensive response to angiotensin-II (Ang-II) infusion. In this study, we examined the effects of PRR deletion in collecting duct (CD) specific mouse models targeting either the principal cells (PC) or intercalated cells (IC). PC-specific PRR knockout (KO) mice were obtained by crossing floxed PRR mice with mice harboring AQP-2 Cre recombinase. Compared to floxed mice, PC specific KO PRR mice had no differences in PRR immunostaining but had 50% reduction in PRR mRNA in micro-dissected cortical CDs. No differences in blood pressure were observed between the two groups at baseline or following Ang-II infusion at 600 ng/kg/min. Similarly, plasma renin concentration and renal expression of ENaC protein isoforms were comparable between the two groups. To achieve IC-specific PRR deletion, floxed PRR mice were bred with mice expressing B-1 Cre recombinase. Compared to floxed controls, IC-specific PRR KO mice were smaller (KO body weight: 5.9 ± 1.3 g vs controls: 11.1± 1.2 g) and did not survive beyond 30 days after birth. IC-specific PRR KO mice also demonstrated marked reduction in renal medullary PRR immunostaining along with decreased renal expression of ENaC-α protein (50% reduction compared to controls), similar to the findings in nephron wide deletion of PRR. Taken together, these findings suggest that IC specific deletion of PRR but not PC-specific deletion modulates renal ENaC expression. Further studies evaluating ENaC activity in isolated cortical CDs from PC and IC specific PRR KO mice will help delineate the functional role of CD PRR in Na + homeostasis.