Antioxidative and blood pressure-lowering effects of Scurrula atropurpurea on deoxycorticosterone acetate–salt hypertensive rats

Acute beta-adrenoreceptor blockade results in an enhanced blood pressure-lowering effect in glucocorticoid hypertensive rats in the absence of the adrenals. To evaluate the possible mechanism of this enhanced blood pressure-lowering effect, systemic and regional hemodynamics were determined by the radioactive microsphere technique before and after propranolol administration in bilaterally adrenalectomized (AX) and sham-operated (SH) glucocorticoid hypertensive rats. Propranolol decreased mean blood pressure (BP) and heart rate (HR) to a greater extent in the AX animals. In response to propranolol, cardiac output (CO) decreased equally in both the AX and SH animals. Regional vascular responses to propranolol were similar between the AX and SH animals, except in muscle. In muscle propranolol significantly decreased blood flow and increased resistance in the SH animals. In marked contrast, in the AX animals propranolol significantly increased blood flow and decreased vascular resistance. The results of this study show that in adrenalectomized glucocorticoid hypertensive rats, the enhanced BP lowering effect of acute beta-adrenoreceptor blockade is not mediated by changes in CO. Additionally, in glucocorticoid hypertensive rats acute beta-adrenoreceptor blockade causes selective vasodilation in skeletal muscle.

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Abstract P760: Plasma Kallikrein Contributes to Intracerebral Hemorrhage and Hypertension in Stroke-Prone Spontaneously Hypertensive Rats

Stroke ◽

10.1161/str.52.suppl_1.p760 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Fabricio Simao ◽

Jian Guan ◽

Allen Clermont ◽

Loc-Duyen Pham ◽

Tuna Ustunkaya ◽

...

Keyword(s):

Blood Pressure ◽

Intracerebral Hemorrhage ◽

Spontaneously Hypertensive Rats ◽

High Salt ◽

Plasma Kallikrein ◽

Spontaneous Intracerebral Hemorrhage ◽

Blood Pressure Lowering ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Pressure Lowering

Introduction: Hypertension is a leading risk factor for spontaneous intracerebral hemorrhage. Plasma Kallikrein (PKa) has been implicated in contributing to hemorrhage following thrombolytic therapy, however, its role in spontaneous intracerebral hemorrhage is currently not available. This report investigates the role of PKa on hemorrhage and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). Methods: SHRSP were fed with a high salt containing stroke-prone diet to increase blood pressure and induce spontaneous intracerebral hemorrhage. The roles of PKa on blood pressure, intracerebral hemorrhage, and survival in SHRSP were examined in rats receiving a PKa inhibitor (BPCCB) or plasma prekallikrein antisense oligonucleotide (PK ASO) compared with rats receiving control ASO. Effects on PKa on the proteolytic cleavage of atrial natriuretic peptide (ANP) were analyzed by tandem mass spectrometry. Results: PKa activity in plasma was increased by 29% in SHRSP on high salt diet compared with control rats. Cleaved kininogen, a substrate for PKa, was 2-fold greater in SHRSP plasma during stroke compared with SHRSP without stroke symptoms. Systemic administration of BPCCB or PK ASO to SHRSP reduced intracerebral hemorrhage (Fig. 1A) and blood pressure (Fig. 1B), and improved neurological function and survival when compared with rats receiving control ASO. Since PKa inhibition was associated with reduced blood pressure in hypertensive rats, we investigated the effects of PKa on the cleavage of ANP. Incubation of PKa with ANP resulted in the generation fragment ANP 5-28 , which displayed reduced effects on blood pressure lowering compared with full length ANP. Conclusions: PKa contributes to increased blood pressure in SHRSP, which is associated with intracerebral hemorrhage and reduced survival. PKa-mediated cleavage of ANP reduces its blood pressure lowering effects and thereby may contribute to hypertension-induced intracerebral hemorrhage.

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