Cardiovascular diseases, especially the hypertension, have been a global threat for the last few decades because of non-curative effects of the available synthetic drugs and their high economic burden on the patients as their treatment requires lifelong use of drugs. Therefore, alternate effective and economical treatment options are urgently needed to be explored from all possible resources. Since ancient times plants have been utilized for treating various ailments and even some drugs have been derived from the traditionally used plants. This part of the world has been blessed with diverse medicinal flora that has been widely used on empirical folkloric basis. Due to these reasons, three medicinal plants claimed to be effective and curative for certain cardiovascular diseases were selected for the present investigations. The study consists of evaluation of antihypertensive, cardiac depressant and vasorelaxant effects of aqueous-methanolic (aq-meth) extracts and certain fractions of three indigenous medicinal plants viz. Sonchus asper, Linn. (aerial-parts), Pennisetum glaucum, Linn. (seeds) and Zanthoxylum armatum, DC. (fruits). The results obtained showed that aq-meth extracts of all three plants have significantly decreased the systolic blood pressure (SBP), mean arterial pressure (MAP) and diastolic blood pressure (DBP) and also reduced the heart rates of normotensive rats in the dose and time dependent manner. Further studies were carried out on the glucose and egg yolk fed hypertensive rats. The aq-meth extracts of all the three test plants were found to significantly prevent the diet-induced rise in blood pressure parameters as well as the heart rates of aq-meth extract treated rats. Acute toxicity study showed safety of the extracts as their LD50s in mice were quite high i.e., 3500 and 3000 mg /kg p.o., for the aq-meth extracts of S. asper and Z. armatum, respectively. While no mortality occurred with oral administration of P. glaucum extract upto 4000 mg/kg dose, so no LD50 was calculated for aq-meth extract of P. glaucum. In subchronic toxicity testing, non-significant changes were observed in liver ezymes and lipid profile parameters of treated rats. These data have clearly demonstrated that the test plants’ extracts do not possess significant amount of toxic substances. Therefore, investigations were further extended to determine their active fraction (s) and possible mechanism (s) of action. For this purpose, aq-meth extracts of S. asper (aerial-parts) and P. glaucum (seeds) were fractionated into ethyl acetate, butanolic and aqueous fractions while a polyphenolic compound, tambulin already reported to be present in Z. armatum (fruits) was isolated for further experiments. In isolated perfused rabbit hearts, the extracts, fractions and tambulin were found to significantly decrease the force of contraction, perfusion pressure and heart rate. Ethyl acetate fraction of S. asper and butanolic fraction of P. glaucum among their tested fractions showed more pronounced effects on the cardiac parameters. Then studies were conducted on porcine coronary artery rings and it was observed that aq-meth extracts, fractions and tambulin produced a dose dependent similar vasorelaxant effects in U46619 pre-contracted endothelium-intact as well as denuded artery rings. However, endothelium removal was not found to significantly affect their vasorelaxant potencies indicating the endothelium-independent effect. Interestingly, the effects of ethyl acetate fraction of S. asper and butanolic fraction of P. glaucum were more marked in this respect, too. Therefore, these fractions were selected for futher study in order to find possible mechanism (s) of their vasorelaxant effects. The tambuin (10 µM) produced 100% relaxation of intact and denuded coronary artery rings and was subjected to further series of experiments along with other potent fractions i.e., ethyl acetate fraction of S. asper and butanolic fraction of P. glaucum. It was observed that the response curves of the endothelium-dependent vasodilating agents including bradykinin and calcum ionophore were not shifted by the test fractions and tambulin showing that their relaxant effect was endothelium-independent and the effect was governed by the vascular smooth muscles. It was also found that ethyl acetate fraction of S. asper (0.01 mg/ml), butanolic fraction (0.03 mg/ml) of P. glaucum and tambulin (1µM) produced shifting of concentration response curves of the endothelium-independent vasodilators including, sodium nitroprusside (SNP), forskolin (FC) and isoproterenol. The experiments also showed that the test fractions and tambulin did not shift response curves produced by soluble guanyly cyclase (sGC) activators (YC-1 and BAY 41-2272) and K+ channel openers (levchromakalim and 1-EBIO). However, pretreatment with EAFS, BFPG and tambulin suppressed in dose dependent fashion the cumulative contractile responses of endothelium-denuded coronary artery rings induced by KCl, 5-HT, CaCl2 and U46619. Further, experiments were carried out to study the role of c-AMP and c-GMP on the vasorelaxant effect of the test fractions and tambulin. Specific inhibitors of PKA and PKG, namely H-89 and Rp-8-br-cyclic GMPS were used to inhibit the c-AMP and c-GMP elevation, respectively. The relaxations produced by the EAFSA and tambulin were observed to have significantly reduced in the coronary artery rings that were exposed to H-89 (10 µM) and Rp-8-br-cyclic GMPS (30 µM) whereas the relaxant effect of the BFPG was more significantly decreased by Rp-8-br-cyclic GMPS as compared to H-89. The qualitative phytochemical studies on the ethyl acetate fraction of Sonchus asper (aerialparts) and butanolic fraction of Pennisetum glaucum (seeds) showed that saponins, terpenoids, flavonoids, tannins and alkaloids are contained by them. HPLC studies of the test fractions showed the existance of quercetin, gallic acid, caffic acid, vanillic acid, and ferulic acid in both the test plants’ fractions where as chlorogenic acid, m-coumaric acid and synapic acid were detected in ethyl acetate fraction of S. asper while p-coumaric acid and ginamic acid were contained in butanolic fraction of the P. glaucum. It is conceivable, therefore, that the test medicinal plants, namely Sonchus asper (aerial-parts), Pennisetum glaucum (seeds) and Zanthoxylum armatum (fruits) empirically used in folkloric medicine to treat various cardiovascular diseases do contain compounds that are able to produce antihypertensive effects. Current findings have also suggested that the reported antihypertensive effect might have resulted from vasorelaxation produced by elevation of c-AMP and/or c-GMP levels in the vasculature. However, inhibition of calcium influx, prevention of calcium mobilization from sarcoplasmic reticulum into the cytoplasm, negative ionotropic and chronotropic effects on the heart and the prevention of the oxidative stress by test fractions could also be responsible for their antihypertensive property. Phytochemical analyses of these plants’ potent fractions have shown that no single chemical compound can be held responsible for the reported activities as several chemical entities have been detected in them. Furthermore, comprehensive chemical and pharmacological studies should be planned to isolate active principles, identify their chemical structure and elucidate exact mechanism (s) of the antihypertensive effect of tested plants. In the meantime, tambulin isolated from Zanthoxylum armatum (fruits) could be suggested as its major active antihypertensive principle. The results substantiate the antihypertensive activity of the indigenous medicinal plants and their fractions. May be here lies the role that the traditional system of medicine has to play in advancing