Vascular Hypertrophy, Renin and Blood Pressure in the Young Spontaneously Hypertensive Rat

Morton, J. J.; Beattie, Elisabeth; Griffin, Sheila A.; MacPherson, Fiona; Lyall, Fiona; Russo, Domenico

doi:10.1042/cs0790523

Cited by 16 publications

(15 citation statements)

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“…In contrast to the present studies in SHR, a significant amelioration of hypertension and renal inflammation has been reported after 3 wk of administration of apocynin in DOCA/salt-treated rats (6). However, in contrast to this model, our rats were studied at an age range (7-10 wk) when blood pressure was still rising, and elevated sympathetic activity and increased vascular contractility primarily determine hypertension in SHR (14,19,24). Secondary changes such as vascular and hormonal alterations typically occurring in older SHR and in the DOCA/salt model had not developed at this time point (4,6,13).…”

Section: Discussioncontrasting

confidence: 73%

Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Paliege

Parsumathy

Mizel

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) synthesize type 1 nitric oxide synthase (NOS1) and type 2 cyclooxygenase (COX-2). Both nitric oxide (NO) and prostaglandins have been considered to mediate or modulate the control of renin secretion. Reactive oxygen species (ROS) produced locally by NADPH oxidase may influence NO bioavailability. We have tested the hypothesis that in hypertension elevated ROS levels may modify the expression of NOS1 and COX-2 in the JGA, thereby interacting with juxtaglomerular signaling. To this end, spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY) received the specific NADPH oxidase inhibitor, apocynin, during 3 wk. Renal functional and histochemical parameters, plasma renin activity (PRA), and as a measure of ROS activity, urinary isoprostane excretion (IP) were evaluated. Compared with WKY, IP levels in untreated SHR were 2.2-fold increased, and NOS1 immunoreactiviy (IR) of JGA 1.5-fold increased, whereas COX-2 IR was reduced to 35%, renin IR to 51%, and PRA to 7%. Apocynin treatment reduced IP levels in SHR to 52%, NOS1 IR to 69%, and renin IR to 62% of untreated SHR, whereas renin mRNA, COX-2 IR, glomerular filtration rate, PRA, and systolic blood pressure remained unchanged. WKY revealed no changes under apocynin treatment. These data show that NADPH oxidase is an important contributor to elevated levels of ROS in hypertension. Upregulation of MD NOS1 in SHR may have the potential of blunting the functional impact of ROS at the level of bioavailable NO. Downregulated COX-2 and renin levels in SHR are apparently unrelated to oxidative stress, since apocynin treatment had no effect on these parameters.

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Section: Discussioncontrasting

confidence: 73%

Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Paliege

Parsumathy

Mizel

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…[4][5][6][7][8]10,11,15,18 In our colony, conscious MAP was not different between SHRs and WKY rats at 4 weeks of age; however, structurally based vascular resistance properties were higher in both 2-and 4-week-old SHRs versus WKY rats. These findings extend our previous results in rats from the same colony and suggest that vascular resistance properties differ to the same extent (ie, Ϸ30%) from neonatal to adult SHRs (Յ50 weeks), whereas the full expression of hypertension in SHRs only appears at Ϸ14 weeks of age.…”

Section: Discussionmentioning

confidence: 90%

Altered Vascular Resistance Properties and Acute Pressure-Natriuresis Mechanism in Neonatal and Weaning Spontaneously Hypertensive Rats

2012

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Abstract-Although it has been extensively scrutinized, the factor(s) involved in the initiation and development of hypertension in spontaneously hypertensive rats (SHRs) remains unresolved. The objective of the present study was to determine whether, early in development, the causal mechanism(s) for the development of hypertension in young SHRs involves an integration of 2 processes, specifically an upregulation of structurally based vascular resistance properties and a rightward shift in the hemodynamic component of pressure-natriuresis. Mean arterial pressure was determined in conscious 4-week-old SHRs and Wistar-Kyoto rats via previously implanted aortic catheters. Structurally based hindlimb vascular resistance properties were assessed in 2-and 4-week-old SHRs and Wistar-Kyoto rats. Renal interstitial hydrostatic pressure was measured after short-term manipulations of renal arterial pressure (RAP) in 4-week-old, anesthetized rats. Although mean arterial pressure in conscious SHRs (113Ϯ5 mmHg) and Wistar-Kyoto rats (110Ϯ6 mmHg) was not significantly different at 4 weeks of age, SHRs at 2 and 4 weeks of age already had increases in structurally based vascular resistance properties of Ϸ30% above age-and weight-matched Wistar-Kyoto rats. Furthermore, the acute RAP-renal interstitial hydrostatic pressure relationship was found to be linear in both strains, and the temporal coupling of the stimulus to response was rapid; that is, renal interstitial hydrostatic pressure responses to changes in RAP were Ͻ2 s. Although the slope of the RAP-renal interstitial hydrostatic pressure relationship was not significantly different between strains, the relationship was significantly shifted (18%) to higher RAPs in SHRs. These results suggest that alterations in both vascular structure and renal function in young SHRs occur before elevations in mean arterial pressure. A lthough the factors responsible for the initiation and development of genetic hypertension have been extensively studied in the spontaneously hypertensive rat (SHR), the basis and time course for blood pressure elevation remain enigmatic. Specifically, what remains controversial is whether the 2 most widely studied processes, vascular abnormalities and renal dysfunction, lead to increases in arterial pressure or vice versa.Since the 1970s, 1 it has been well established that vascular abnormalities, such as increases in vascular resistance, vascular reactivity to vasoconstrictors, and media:lumen ratio, are associated with hypertension in the adult SHR.1-3 Despite the number of studies describing vascular morphometric and histological differences in young SHRs, 4-9 evidence linking blood pressure elevations with vascular structural and functional changes remains unresolved in the neonatal and weaning SHRs. The hypothesis that vascular structural changes antecede and initiate a rise in arterial pressure has been disputed for 2 main reasons, the presence 8,10-13 or lack 4-7,9,14,15 of blood pressure elevation in studies of young SHRs and substantial differences be...

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“…This was measured as previously described [ 12]. Briefly, rats were killed by a blow to the head and cervical dislocation.…”

Section: Resistance Artery Structurementioning

confidence: 99%

“…The order of study was randomized and unknown to the operator. The mi/l, ratio was calcu lated for individual segments and the mean value obtained for the 3-4 segments taken from each rat [ 12],…”

Section: Resistance Artery Structurementioning

confidence: 99%

Angiotensin II Receptor Antagonist Losartan Has Persistent Effects on Blood Pressure in the Young Spontaneously Hypertensive Rat: Lack of Relation to Vascular Structure

Morton

Beattie

MacPherson³

1992

J Vasc Res

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111

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The persistent effects on blood pressure of the angiotensin II receptor antagonist losartan and the converting enzyme inhibitor captopril were compared in the young spontaneously hypertensive rat (SHR). Losartan (DuP753/MK954, 15 mg/kg/day) and captopril (100 mg/kg/day) were given in the drinking water of 3-week-old SHRs for 4- and 10-week durations. Blood pressure was measured during treatment and after treatment was stopped until the age of 30 weeks. Both losartan and captopril given for 4 and 10 weeks prevented the development of hypertension during treatment and redevelopment of hypertension after treatment was stopped. Treatment for 10 weeks was more effective than for 4 weeks in lowering long-term pressure. Four weeks of treatment did not affect the mesenteric resistance artery media/lumen (m₁/l₁) ratio. In contrast, both losartan and captopril given for 10 weeks resulted in large and significant reductions in m₁/l₁ [5.3 ± 0.8 and 5.63 ± 0.8 vs 7.7 ± 0.8 × 10^-2 (SD), p < 0.001]. In losartan-treated rats, plasma renin and angiotensin II concentration were increased between 4- and 7-fold at the end of both treatment periods. These findings show losartan to be an effective antihypertensive agent and support data implicating angiotensin II in the early events leading to hypertension in this model. The abilities of losartan and captopril to affect blood pressure without affecting vascular structure suggest that the latter is a poor predictor of long-term hypertensive levels in the SHR.

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Vascular Hypertrophy, Renin and Blood Pressure in the Young Spontaneously Hypertensive Rat

Cited by 16 publications

References 0 publications

Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Altered Vascular Resistance Properties and Acute Pressure-Natriuresis Mechanism in Neonatal and Weaning Spontaneously Hypertensive Rats

Angiotensin II Receptor Antagonist Losartan Has Persistent Effects on Blood Pressure in the Young Spontaneously Hypertensive Rat: Lack of Relation to Vascular Structure

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