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The hemodynamic effects of ANF (1 and 5 micrograms/kg/min) and its potential interactions with the sympathetic system were investigated at the systemic and regional (pulsed Doppler) levels in the pithed SHR. ANF dose-dependently decreased cardiac output CO, renal (RBF), mesenteric (MBF) and hindquarter (HQBF) blood flows and increased the corresponding vascular resistances: total peripheral (TPR), renal (RR), mesenteric (MR) and hindquarter (HQR), all these effects being significant at 5 micrograms/kg/min. Mean blood pressure (MBP) and heart rate were also significantly decreased at 5 micrograms/kg/min. ANF significantly reduced the responses to cirazoline of MBP, TPR and RR (1 microgram/kg/min) and of MR (5 micrograms/kg/min) but did not affect those of HQR ANF also significantly reduced the responses to UK-14,304 of MBP, TPR and MR (5 micrograms/kg/min) but did not affect those of RR and HQR. These data indicate that (a) ANF, in the absence of reflex phenomenons, exerts intrinsic regional vasoconstrictor effects, (b) ANF exhibits a postsynaptic sympatho-inhibitory effect. The latter is more marked vs the alpha 1-(especially renal) than vs the alpha 2-adrenoceptor-mediated responses but does not affect the hindquarter vascular bed, which suggest that its contribution to the overall antihypertensive action of ANF is of limited importance.

The systemic and regional (kidney, mesentery, hindlimb) hemodynamic effects of (a) two potassium agonists: cromakalim (1 to 8 micrograms.kg-1.min-1/15 min) and SR 44866 (0.125 to 2 micrograms.kg-1.min-1/15 min) and (b) a calcium antagonist, nicardipine (0.5 to 2 micrograms.kg-1.min-1/15 min) have been investigated by the pulsed doppler technique, and compared in the anesthetized normotensive rat. The two potassium agonists and nicardipine lowered blood pressure (BP) and total peripheral resistance (TPR) dose-dependently and slightly increased heart rate. Cardiac output (QC) remained unchanged. SR 44866 was as potent as nicardipine in reducing BP and about three to four times more potent than cromakalim (the DE20s, doses producing a 20 p. 100 decrease in BP, being: SR 44866: 0.7 micrograms.kg-1.min-1, cromakalim: 2.8 micrograms.kg-1, nicardipine: 0.8 micrograms.kg-1.min-1). At these equihypotensive doses, the three drugs (a) similarly decreased TPR (SR 44866: -16 p. 100, cromakalim: -17 p. 100, nicardipine: -19 p. 100, (b) reduced mesenteric vascular resistance (MVR) (SR 44866: -18 p. 100, cromakalin: -20 p. 100, nicardipine: -21 p. 100) and renal vascular resistance (RVR) (SR 44866: -16 p. 100, cromakalim: -21 p. 100, nicardipine: -13 p. 100 to the same extent as TPR, but (c) SR 44866 and nicardipine reduced hindlimb vascular resistance (HVR) to a larger extent than TPR (SR 44866: -25 p. 100, nicardipine: -25 p. 100.(ABSTRACT TRUNCATED AT 250 WORDS)

MK 421, 25 mg/kg, administered daily by gavage to young spontaneously hypertensive rats (SHRs) from their 4th to 15th weeks of age almost completely inhibited genetic hypertension development. Since heart rate and cardiac index were not drug affected, prevention of genetic hypertension development was solely related to an early, potent and long-lasting limitation of the progressive increase in peripheral resistance which normally develops in SHRs during ageing. MK 421 slightly enhanced vascular responsiveness to exogenous norepinephrine and angiotensin II and reduced myocardial hypertrophy. Plasma renin concentration was increased. MK 421 slightly reduced body growth but did not affect fluid intake, urinary volume and urinary ADH, demonstrating that no water or salt retention developed. Finally, MK 421's preventive effects against genetic hypertension development persisted up to 10 weeks after treatment discontinuation.