Dataset Information

BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats.

ABSTRACT:

Background

Renal autoregulation maintains stable renal function despite BP fluctuations and protects glomerular capillaries from hypertensive injury. However, real-time dynamics of renal autoregulation in conscious animals have not been characterized.

Methods

To develop novel analytic methods for assessing renal autoregulation, we recorded concurrent BP and renal blood flow in conscious rats, comparing animals with renal autoregulation that was intact versus impaired (from 3/4 nephrectomy), before and after additional impairment (from the calcium channel blocker amlodipine). We calculated autoregulatory indices for adjacent short segments of increasing length (0.5, 1, 2.5, 5, 10, and 20 seconds) that exhibited a mean BP difference of at least 5 mm Hg.

Results

Autoregulatory restoration of renal blood flow to baseline after BP changes in conscious rats occurs rapidly, in 5-10 seconds. The response is significantly slower in states of impaired renal autoregulation, enhancing glomerular pressure exposure. However, in rats with severe renal autoregulation impairment (3/4 nephrectomy plus amlodipine), renal blood flow in conscious animals (but not anesthetized animals) was still restored to baseline, but took longer (15-20 seconds). Consequently, the ability to maintain overall renal blood flow stability is not compromised in conscious rats with impaired renal autoregulation.

Conclusions

These novel findings show the feasibility of renal autoregulation assessment in conscious animals with spontaneous BP fluctuations and indicate that transient increases in glomerular pressure may play a greater role in the pathogenesis of hypertensive glomerulosclerosis than previously thought. These data also show that unidentified mechanosensitive mechanisms independent of known renal autoregulation mechanisms and voltage-gated calcium channels can maintain overall renal blood flow and GFR stability despite severely impaired renal autoregulation.

SUBMITTER: Bidani AK

PROVIDER: S-EPMC7003298 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats.

Bidani Anil K AK Polichnowski Aaron J AJ Licea-Vargas Hector H Long Jianrui J Kliethermes Stephanie S Williamson Geoffrey A GA Griffin Karen A KA

Journal of the American Society of Nephrology : JASN 20191202 2

<h4>Background</h4>Renal autoregulation maintains stable renal function despite BP fluctuations and protects glomerular capillaries from hypertensive injury. However, real-time dynamics of renal autoregulation in conscious animals have not been characterized.<h4>Methods</h4>To develop novel analytic methods for assessing renal autoregulation, we recorded concurrent BP and renal blood flow in conscious rats, comparing animals with renal autoregulation that was intact versus impaired (from 3/4 nep ...[more]

PMID: 31792155

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Project description:Although physiological responses to hemorrhage are well-studied, hemorrhage is often accompanied by trauma, and it remains unclear how injury affects these responses. This study examined effects of extremity trauma on cardiorespiratory responses and survival to moderate (37%; H-37) or severe (50%; H-50) hemorrhage in rats. Transmitter and carotid catheter implantation and extremity trauma (fibular fracture and muscle injury) were conducted 2 wk, 24 h, and 90 min, respectively, before conscious hemorrhage. Mean arterial pressure (MAP) and heart rate (HR; via telemetry), and respiration rate (RR), minute volume (MV), and tidal volume (TV; via plethysmography) were measured throughout the 25 min hemorrhage and remainder of the 4 h observation period. There were four groups: 1) H-37, no trauma (NT; n = 17); 2) H-37, extremity trauma (T, n = 18); 3) H-50, NT (n = 20); and 4) H-50, T (n = 20). For H-37, during and after hemorrhage, T increased HR (P ≤ 0.031) and MV (P ≤ 0.048) compared with NT rats. During H-50, T increased HR (0.041) and MV (P = 0.043). After hemorrhage, T increased MV (P = 0.008) but decreased HR (P = 0.007) and MAP (P = 0.039). All cardiorespiratory differences between T and NT groups were intermittent. Importantly, both survival time (159.8 ± 78.2 min vs. 211.9 ± 60.3 min; P = 0.022; mean ± SD) and percent survival (45% vs. 80%; P = 0.048) were less in T versus NT rats after H-50. Trauma interacts with physiological systems in a complex manner and no single cardiorespiratory measure was sufficiently altered to indicate that it alone could account for increased mortality after H-50.NEW & NOTEWORTHY In both civilian and military settings, severe hemorrhage rarely occurs in the absence of tissue trauma, yet many animal models for the study of hemorrhage do not include significant tissue trauma. This study using conscious unrestrained rats clearly demonstrates that extremity trauma worsens the probability of survival after a severe hemorrhage. Although no single cardiorespiratory factor accounted for the increased mortality, multiple modest time-related cardiorespiratory responses to the trauma were observed suggesting that their combined dysfunction may have contributed to the reduced survival.

Dataset Information

BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats.

Background

Methods

Results

Conclusions

Publications

BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats.

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