Chronic antihypertensive drug treatment in young spontaneously hypertensive rats: effects on arterial blood pressure, cardiovascular reactivity and vascular design

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Abstract
To investigate the effect of early prolonged antihypertensive treatment on arterial pressure and vascular design in primary hypertension, male spontaneously hypertensive rats were treated between 3 weeks and 10 months of age with propranolol, metoprolol, hydralazine, or guanethidine and hydralazine in combination. Untreated matched spontaneously hypertensive rats were used as controls. At the end of the treatment period the rats were exposed to standardised ‘stressful’ stimuli such as flashing light, loud noise, and vibrations, while changes in heart rate and mean arterial pressure were continuously measured. Finally the hindquarters were perfused at constant flow in parallel with those of a normotensive control rat and the full range of resistance responses to infused noradrenaline was explored as earlier described (Folkow et al., 1970). Mean dose-response ‘resistance curves’ were then constructed for each paired group and compared for resistance at maximal dilatation, gradient of the curve, and maximal pressor response, which together reflect the structural characteristics of the resistance vessels. Compared with controls, the acute pressor responses to ‘stress’ stimulation were reduced by all drugs, except propranolol which rather enhanced them, presumably because adrenaline vasodilatation was in this case reversed to overall vasoconstriction. Resting mean arterial pressure was considerably reduced by all types of treatment used but, like the left ventricular hypertrophy (Weiss and Lundgren, 1978) the hypertensive structural changes of the resistance vessels appeared to be more pronounced than the actual mean arterial pressure levels would suggest. This inability to fully prevent structural cardiovascular changes in spontaneously hypertensive rats even by early pharmacological mean arterial pressure normalisation, may suggest that the genetical predisposition in spontaneously hypertensive rats involves the cardiovascular effectors themselves, eg by trophic influences facilitating early muscle hyperplasia.