What question did this study set out to answer?

To determine whether tissue converting enzyme (CE) inhibition correlates with the antihypertensive efficacy of two distinct CE inhibitors, Hoe498 and MK421, in hypertensive rat models.

September 1, 1984Journal of Cardiovascular Pharmacology

Is Tissue Converting Enzyme Inhibition a Determinant of the Antihypertensive Efficacy of Converting Enzyme Inhibitors? Studies with the Two Different Compounds, Hoe498 and MK421, in Spontaneously Hypertensive Rats

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Why the study?

Does tissue converting enzyme inhibition determine the antihypertensive efficacy of converting enzyme inhibitors in spontaneously hypertensive rats?

Population

Spontaneously hypertensive rats (SHRSP)

Comparison

Oral converting enzyme inhibitors Hoe498 and… vs Comparison between Hoe498 and MK421

Design

Preclinical

Follow-up

2 and 4 weeks

Authors

TUThomas UngerGeneral Cardiology DGDetlev GantenGeneral / Preventive / Lipids RLR. LangUniversity of Bern

Discussion

Member takes

Implication

Supports tissue CE inhibition in CEI efficacy in rat models; leaves open human translation and clinical relevance.

Key Points

To determine whether tissue converting enzyme (CE) inhibition correlates with the antihypertensive efficacy of two distinct CE inhibitors, Hoe498 and MK421, in hypertensive rat models.
Treated spontaneously hypertensive rats (SHRSP) orally with Hoe498 or MK421 for durations of 2 and 4 weeks.
Measured blood pressure responses alongside circulating markers (plasma angiotensin II, urinary aldosterone, intravenous/central angiotensin I pressor responses, and bradykinin responses).
Evaluated tissue CE activity across the aorta, lung, kidney, heart, adrenal gland, and brain cortex following equi-dose treatments (10 mg/kg/day).
Hoe498 showed higher antihypertensive potency than MK421, normalizing blood pressure at 10 mg/kg/day versus 30 mg/kg/day, with threshold doses below 0.1 mg/kg/day versus 1 mg/kg/day.
Plasma angiotensin II levels, urinary aldosterone excretion, and vascular responses to intravenous angiotensin I or bradykinin did not correlate with antihypertensive potency.
Equi-dose Hoe498 achieved significantly greater tissue CE inhibition in the vascular wall, lung, kidney, heart, adrenal gland, and brain cortex than MK421.

Structured PICO

Does tissue converting enzyme inhibition determine the antihypertensive efficacy of converting enzyme inhibitors in spontaneously hypertensive rats?

Population

Spontaneously hypertensive rats (SHRSP)

Intervention

Oral converting enzyme inhibitors Hoe498 and MK421 for 2 and 4 weeks

Comparator

Comparison between Hoe498 and MK421

Outcome

Blood pressure reduction and tissue converting enzyme activitysurrogate

Tissue converting enzyme inhibition in target organs such as the vascular wall, kidney, heart, and brain is likely involved in the antihypertensive action of CE inhibitors.

Cite This Study

Unger et al. (1984) studied this question.

synapsesocial.com/papers/6a7d3de22935e92dbc775e30 https://doi.org/10.1097/00005344-198409000-00021

Topics

Hypertension management

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Is Tissue Converting Enzyme Inhibition a Determinant of the Antihypertensive Efficacy of Converting Enzyme Inhibitors? Studies with the Two Different Compounds, Hoe498 and MK421, in Spontaneously Hypertensive Rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Is Tissue Converting Enzyme Inhibition a Determinant of the Antihypertensive Efficacy of Converting Enzyme Inhibitors? Studies with the Two Different Compounds, Hoe498 and MK421, in Spontaneously Hypertensive Rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Topics

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