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Delayed development of hypertension after short-term nitrendipine treatment
D Rizzoni1, M Castellano, E Porteri
1Cattedra di Semeiotica e Metodologia Medica, U.O.P. Scienze Mediche, University of Brescia, Italy.
Abstract:
In this study we evaluated the delayed effects of a calcium entry blocker on blood pressure and on vascular structural and functional alterations in mesenteric resistance arteries of spontaneously hypertensive rats (SHR). The calcium entry blocker nitrendipine was administered (30 mg/kg per day) according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 12), and in a third group from 4 to 12 weeks of age (n = 12). Twelve untreated SHR and 12 untreated Wistar-Kyoto rats served as controls. Half the animals of each group were killed at 13 weeks, and the remaining were killed at 38 weeks. After death, relative left ventricular mass was calculated. Vascular morphology and function (responses to norepinephrine and acetylcholine) in mesenteric small arteries were then assessed using a micromyographic technique. Nitrendipine treatment delayed the development of hypertension and determined the regression of structural alterations of mesenteric resistance arteries in SHR. These favorable effects were maintained for several weeks after treatment withdrawal, provided that treatment was started at 4 weeks of age. Considering the functional alterations of mesenteric arteries in SHR (responses to norepinephrine and acetylcholine), nitrendipine treatment determined an improvement of both these dysfunctions as long as reductions of the media-to-lumen ratio and blood pressure, respectively, were maintained.
Insights
Nitrendipine, a calcium entry blocker, delayed hypertension and improved vascular structure in rats. Early treatment initiated at 4 weeks showed lasting benefits even after withdrawal, highlighting its potential for long-term cardiovascular health.
Area of Science:
- Cardiovascular Pharmacology
- Hypertension Research
- Vascular Biology
Background:
- Spontaneously hypertensive rats (SHR) exhibit significant vascular structural and functional alterations.
- Hypertension in SHR is associated with increased media-to-lumen ratio and impaired vascular responses.
- Calcium entry blockers are a key therapeutic class for managing hypertension.
Purpose of the Study:
- To evaluate the delayed effects of nitrendipine on blood pressure.
- To assess nitrendipine's impact on vascular structural and functional changes in mesenteric arteries of SHR.
- To determine if early-onset nitrendipine treatment offers sustained cardiovascular benefits.
Main Methods:
- Nitrendipine was administered to SHR at different ages (4-8, 8-12, 4-12 weeks) and doses (30 mg/kg/day).
- Vascular morphology, function (responses to norepinephrine and acetylcholine), and cardiac mass were assessed via micromyography.
- Animals were studied at 13 and 38 weeks of age, with untreated SHR and Wistar-Kyoto rats as controls.
Main Results:
- Nitrendipine treatment delayed hypertension development in SHR.
- The drug induced regression of structural alterations in mesenteric resistance arteries.
- Favorable effects on vascular structure and function persisted post-treatment, particularly when initiated early (4 weeks).
Conclusions:
- Early administration of nitrendipine in SHR can delay hypertension and reverse vascular damage.
- Sustained cardiovascular benefits are achievable with early intervention, even after drug cessation.
- Nitrendipine improves vascular dysfunction by reducing media-to-lumen ratio and blood pressure.